Category Archives: Gene Medicine

Dr. Nigma Talib Four Seasons Los AngelesWhile Dr. Nigma Talib is a newcomer to the United States, her London skin-care clinic has a several-months-long waiting list. We expect it wont take long for a similar queue to form at the Four Seasons Los Angeles at Beverly Hills, where she started practicing in September. Her face treatments get under way with a consultation (she is a naturopathic physician), during which she inquires about any underlying skin woes and recommends nutritional solutions for a healthier visage. Nearly all of her treatments incorporate high-tech elementssuch as LED paddles for pushing vitamins, peptides, and hyaluronic acid deeper into the skinand are backed by proprietary research. Talibs signature platelet-rich-plasma microneedling procedure adds plant stem cells and activates the skins own collagen synthesis to repair damage and boost elasticity ($550-$1,200).

Craig Venter Health Nucleus Many of the best hospitals in the country offer top-notch executive health programs, where clients spend a day undergoing a battery of health diagnostic tests, but Craig Venters Health Nucleus in San Diego adds a full genetic workup to the typical roster of state-of-the-art MRIs, 3-D heart imaging, and other tests. Venter, who launched the Health Nucleus physical in early 2016, is one of the premier genetic scientists in the world, and his team of physicians can help interpret the results of the testing in a way that is accessible for the layperson. Have a deletion on your RECQL gene? Venters team will tell you if there is any recent or known research on that anomaly and how it might impact your future health, if at all. They will even reach out in subsequent months and years to update you on any new studies that relate to something in your genetic makeup. Test results are presented in an analog binder as well as a digital document ($25,000).

Dr. John Lombard LifeSpan MedicineLifeSpan Medicine neurologist John Lombard hears constantly from his patients that their memories arent as sharp as they used to be. So last January, he and Dr. Chris Rennafounder of the concierge practice, which has offices in Dallas, Los Angeles, and New York Citylaunched a dedicated brain-health track for LifeSpans members. The service can be effective for everything from improving memory and productivity to treating mood and sleep conditions, migraines, and early dementiaeven managing brain injuries, tumors, and degenerative disorders. After a comprehensive neurological assessment, treatment plans typically run from 3 to 6 months with the goals of a return to wellness and prevention of disease. Lombard is an expert at determining the precise scan to order for a specific concern, and he often drills down to the cellular or genetic level to connect defects there to the brains biology and chemistry. He is a firm believer in evidential science but isnt afraid to take avant-garde (but still scientifically sound) approaches to brain healthsuch as improving blood flow to the brain or reducing high cortisol levels as interventions in early cognitive decline ($750$25,000).

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Beauty, Wellness, and Your Brain: 3 Best of the Best Healthcare Heroes - Robb Report

In science and medicine the terminology applied can be the difference between life and death, success and failure. Words have precise meanings, and a productive dialogue in the sciences requires adherence to a common set of mutually recognized terms. Shared meaning is like a verbal handshake that ensures a positive connection where information can flow.

Genetic engineering, familiarly known by the slippery colloquialism GMO, has been central to the production of drugs like insulin, enzymes used in cheese making, and laboratory-produced fibers. The widest-recognized successes have been the adoption of the technology by 20 million farmers onto almost half a billion acres of farmland, most of those in the developing world. Some 70 percent of grocery store products now contain ingredients from genetically engineered plants. And while scientists and farmers acknowledge concerns arising from the overuse of the technology, such as weed and insect resistance, there remains zero credible evidence of health-related concerns.

Still the most beautiful and altruistic applications of this technology remain to be deployed. The innovations geared to solve specific issues in hunger, environment or consumer health have not left university laboratories or government greenhouses.

This cutting edge has not been dulled due to technical problems or clandestine dangers. Instead, technology has been stalled because of high deregulation costs and negative public perception founded on misinformation.

Could part of the problem simply be the bad branding of a good technology? Our social psyche has been saturated with fear-based manufactured risk and misinformation. Could cleaning up our vocabulary advance the publics understanding of the science and help illuminate its actual risks and benefits, while curing the tales of fear mongering?

Goodbye, GMO

Take for instance the abbreviation GMO. The term appears to have been first used thirty-three years ago this week, appropriately in the New York Times, a venue that regularly uses language to blur scientific reality in food space. Over the last decades the term has been adopted as nomenclature of derision; after all, who would want to feed their child an alien organism?

GMO is not a scientific term. Scientifically speaking, genetic modification is ambiguous, applying to many situations. Genetic modification is what happens upon a sexual crossing, mutation, multiplication of chromosomes (like in a seedless watermelon or banana), introduction of a single new gene from an unrelated species or the tweaking a genome with new gene editing techniques. These are all examples of genetic modification, but not all offer the predictability and precision of the process of genetic engineering.

This is why actual scientists rarely (if ever) use the GMO designation in technical parlance. It first regularly was highlighted in rhetoric opposing the technology, and since has sadly been adopted by mainstream media. Works that apply the term tend to disparage the technology, and opt for GMO rather than a scientifically precise term to stoke the negative perception.

For instance, the term GMO is prominently presented in the 2012 publication (retracted) by French biologist Gilles-Erich Seralini and colleagues, juxtaposed with tumor-ridden suffering animals. Their intent was to label the sad and grotesque figures of suffering animals with the three letters, G-M-O. A valid scientific effort would have labeled a figure with the gene installed that made the plant unique, not a catch-all term for an engineered plant. Seralinis work met tremendous outcry from a scientific community that saw this as being a political and manipulative use of the scientific literature to advance an agenda.

The use of the term GMO in the figures is consistent with that interpretation.

In order to help advance the public discussion, we should agree to abandon the meaningless term GMO. This is especially important for academics, scientists, farmers, dietitians and physiciansprofessionals the public relies upon to answer questions about food and farming. It is time for the science-minded community to adopt a common vocabulary to enhance effective discussion and enjoy more meaningful dialogue.

Toward a new phrasebook

Here are my suggestions for how we can adopt a common vocabulary to make sure were all speaking the same language about these technologies.

1. Stop using GMO. It is imprecise. Everything not arising as a clone is genetically modified from previous forms, as is anything changed by mutation. You are a unique genetic modification of your parents combined genes. A dachshund is a genetic modification of an ancestral gray wolf. Instead we should replace GMO with Genetic Engineering. Genetic engineering is adding, subtracting, or adjusting genes in the lab that change a trait in the resulting plant, animal or microbe. It satisfies the very definition of engineering the application of science and mathematics to affect properties of matter or the sources of energy in nature to be made useful to people.

However, the term GMO is something people recognize. Effective communication depends on shared meaning, so scientists or journalists should use the term once in a presentation or article parenthetically, then switch to genetic engineering. Experts should make it clear that GMO is not an acceptable term when discussing science.

The flawed GMO must also still be included in keywords, image tags, or in any online content. If it is not present, someone searching the internet for credible information with this non-scientific term may encounter a higher proportion of scientifically questionable information. Providing a parenthetical mention or brief reference ensures that those seeking science-based answers can find them.

2. An All-Encompassing Term. A better term for the scientific processes used to produce new varieties or breeds, or the intermediate steps, would be best referred to as crop or animal genetic improvement. In other words, when we use traditional breeding methods to make plants or animals better, it takes many steps and lots of selection. Thats genetic improvement, whether it is done by sexual exchange, breaking DNA strands with radiation or doubling chromosomes with chemistry.

3. The Newest Technologies. New technologies are now being used that allow scientists to make incredibly specific changes to DNA sequence, without leaving foreign DNA sequences (that some find objectionable) behind. These techniques should be collectively referred to as gene editing. Especially avoid referring to the technology by its technical name like CRISPR/Cas 9 or TALEN, which are specific types of gene editing. It is important because the list of gene editing methods is inevitably growing. Gene editing is also more precise than the often-used genome editing.

The purpose of this brief new glossary is not to provide a mandate based on my narrow experience and observations. Instead, my goal is to offer a proposal so a scientific community eager to precisely engage the public can challenge the pros and cons of these terms to hone an optimal vocabulary. My hope is to ultimately derive an agreed-upon terminology that can be adopted and consistently applied by experts in science, medicine and agriculture. Journalists and science communications may then adopt the precise wording of the discipline for improved precision in communication.

Concrete, unambiguous terms can help curious and concerned people understand the realities of genetic engineering. Certainly medicine has benefited from precise language, such as how childhood cognitive disabilities are now characterized with greater sensitivity and improved medical precision. This change improved social stigma of various developmental disorders, brought compassionate understanding to the conditions, and enhanced treatment for those affected.

Better scientific literacy and precision in terminology around genetic engineering would lead to a more productive discourse that ultimately could enable more rapid deployment of safe technologies that can help people and the planet. The individuals that insist on adhering to antiquated, divisive and imprecise terms will be automatically characterized as antiquated, divisive and imprecise.

The first step is to stop using the archaic, imprecise term GMO.

Kevin Folta is a land-grant scientist exploring ways to make better food with less input, and how to communicate science. This article was published with his permission. All of Dr. Foltas funding can be found at kevinfolta.com/transparency.

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Kevin Folta: Please say no to the term 'GMO' - AGDAILY

Some bodily activities, sleeping, for instance, mostly occur once every 24 hours; they follow a circadian rhythm. Other bodily functions, such as body temperature, cognitive performance and blood pressure, present an additional 12-hour cycle, but little is known about the biological basis of their rhythm. A team of scientists from various institutions, including Baylor College of Medicine, has revealed that, in addition to 24-hour clocks, mammals and other organisms have 12-hour clocks that are autonomous, work independently from 24-hour clocks and can be modified by external factors. Studying 12-hour clocks is important because altered 12-hour cycles have been linked to human disease. The study appears in Cell Metabolism.

Our lab has been working on how the 24-hour cycles are regulated, and we and others have shown that disturbing these clocks may lead to diseases of metabolism, said senior author Dr. Bert OMalley, chair and professor of molecular and cellular biology and Thomas C. Thompson Chair in Cell Biology at Baylor College of Medicine. For instance, experimental evidence shows that night-shift workers who periodically change their night and day shifts or people who travel overseas often alter their sleep cycles, and this seems to make them prone to gain weight and develop diabetes and other alterations of metabolism that may lead to disease. Its not a good idea to disturb the circadian rhythm on a regular basis.

In addition to physiological activities that cycle every 24 hours, mammals and other organisms have activities that repeat every 12 hours. For example, it has been reported that blood pressure, body temperature, hormone levels and response to therapy fluctuate in 12-hour cycles. In addition, altered 12-hour cycles have been associated with human diseases. Other researchers had identified about 200 genes that are activated in 12-hour cycles. In this study, OMalley and his colleagues set out to determine whether there was a larger number of 12-hour genes and whether their cycles followed the definition of a biological clock, that is whether they worked autonomously and their oscillation could be adjusted by the environment.

Math meets biology to indentify the bodys internal clocks

Dr. Bokai Zhu, first author of this study and a postdoctoral fellow in the OMalley lab, carried out biological analyses to determine the activity of thousands of mice genes in time. Then, co-author Dr. Clifford Dacso, professor of molecular and cellular biology at Baylor College of Medicine, and co-author and mathematician Dr. Athanasios Antoulas, professor of electrical and computer engineering at Rice University, applied mathematical analyses to these biological data.

We were surprised to identify more than 3,000 genes that were expressed following 12-hour rhythms. A large portion of these genes was superimposed on the already known 24-hour gene activities, Zhu said.

The 12-hour clock is autonomous and can be synchronized by external cues

Further work showed that the 12-hour rhythms of genetic activity work as biological clocks. They occur regularly and autonomously in the cells, and their oscillation can be synchronized by certain external stimuli. OMalley and colleagues discovered that 12-hour clocks are independent from 24-hour clocks. When they experimentally eliminated a 24-hour clock, 12-hour clocks continued ticking. Furthermore, the external cues that can synchronize 24-hour clocks, such as sunlight, do not affect 12-hour clocks.

Of all the genes we analyzed, two sets with 12-hour cycles stood out; those involved with protein quality control and processing, which mainly occur in a cellular structure called endoplasmic reticulum, and those related to the energy supply of the cell, which involves the mitochondria, Zhu said. The activities of the endoplasmic reticulum and mitochondria depend on each other, and we have shown here that the 12-hour genes in the endoplasmic reticulum are synchronized with the 12-hour genes in the mitochondria, which provide the energy needed for protein processing.

In addition, we found that certain liver conditions are associated with disturbed 12-hour gene expression in mice. We anticipate that further study of 12-hour cycles might lead to opportunities to improve prevention of or treatments for diseases of the liver and other organs in the future, OMalley said.

Other contributors to this work include Qiang Zhang, Yinghong Pan, Emily M. Mace and Brian York. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, Rice University, the University of Houston and the Max Planck Institute.

This research was supported by grants from the NationaI Institutes of Health (U24 DK097748 and R01 HD07857), the Brockman Foundation, the Center for Advancement of Science in Space, Peter J. Fluor Family Fund, Philip J. Carroll, Jr. Professorship, Joyce Family Foundation, the National Science Foundation Grant CCF-1320866 and the German Science Foundation Grant AN-693/1-1.

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12-hour biological clock coordinates essential bodily functions - Baylor College of Medicine News (press release)

A consultant studies a mammogram. The drug olaparib could slow cancer growth by three months, researchers have found. Photograph: Rui Vieira/PA

A type of inherited and incurable breast cancer that tends to affect younger women could be targeted by a new therapy, researchers have found.

A small study presented at the worlds largest cancer conference found treating patients with the drug olaparib could slow cancer growth by three months and be less toxic for patients with inherited BRCA-related breast cancer.

Researchers said there was not enough data to say whether patients survived longer as a result of the treatment.

We are in our infancy, said Dr Daniel Hayes, president of the American Society of Clinical Oncology and professor of breast cancer research at the University of Michigan. This is clearly an advance; this is clearly proof of concept these can work with breast cancer.

Does it look like its going to extend life? We dont know yet, he said.

The drug is part of the developing field of precision medicine, which targets patients genes to tailor treatment.

It is a perfect example of how understanding a patients genetics and the biology of their tumor can be used to target its weaknesses and personalize treatment, said Andrew Tutt, director of the Breast Cancer Now Research Centre at The Institute of Cancer Research.

Olaparib is already available for women with BRCA-mutant advanced ovarian cancer, and is the first drug to be approved that is directed against an inherited genetic mutation. The study was the first to show olaparib can slow growth of inherited BRCA-related breast cancer. The drug is not yet approved for that use.

People with inherited mutations in the BRCA gene make up about 3% of all breast cancer patients, and tend to be younger. The median age of women in the olaparib trial was 44 years old.

BRCA genes are part of a pathway to keep cells reproducing normally. An inherited defect can fail to stop abnormal growth, thus increasing the risk of cancer. The study examined the effectiveness of olaparib against a class of BRCA-related cancers called triple negative. Olaparib is part of a class of four drugs called PARP-inhibitors that work by shutting down a pathway cancer cells use to reproduce.

The study from Memorial Sloan Kettering Cancer Center in New York randomly treated 300 women with advanced, BRCA-mutated cancer with olaparib or chemotherapy. All the participants had already received two rounds of chemotherapy.

About 60% of patients who received olaparib saw tumors shrink, compared with 29% of patients who received chemotherapy. That meant patients who received olaparib saw cancer advance in seven months, versus four months for only chemotherapy.

Researchers cautioned it is unclear whether olaparib extended life for these patients, and that more research was needed to find out which subset of patients benefit most from olaparib.

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New therapy offers hope against incurable form of breast cancer - The Guardian

SATURDAY, June 3, 2017 (HealthDay News) -- An experimental drug that targets a specific gene mutation can battle a range of advanced cancers in adults and children, researchers are reporting.

The genetic abnormality is known as a TRK fusion, and it's found in only a small percentage of all cancers. So the drug, called larotrectinib, is no panacea.

But researchers found that among 50 patients with TRK fusions, 76 percent saw their cancer regress after starting larotrectinib -- regardless of their age or type of cancer.

For most of those patients -- 79 percent -- the response has lasted at least one year, according to lead researcher Dr. David Hyman.

"There are few therapies that have had that kind of success for patients like these," said Hyman, an oncologist at Memorial Sloan Kettering Cancer Center in New York City.

Dr. William Oh, an oncologist who was not involved in the study, agreed.

"A 76 percent response rate for a new drug is extremely exciting," said Oh, chief of hematology and medical oncology at the Icahn School of Medicine at Mount Sinai in New York City.

"More importantly," he added, "the responses have been durable, lasting over a year -- which for some of these aggressive cancers is very promising."

This is the latest drug to target flaws in genes that occur anywhere in the body instead of just going after an organ-specific tumor. The first drug to work this way -- Keytruda (pembrolizumab) -- was approved for targeted use by the U.S. Food and Drug Administration on May 24. (Keytruda had previously received traditional FDA-approval for some organ-specific cancers.)

Targeted therapies are designed to zero in on specific abnormalities found on tumor cells -- with the aim of killing off the cancer while sparing healthy cells.

The patients in Hyman's study had a range of cancers, including colon, lung, pancreatic and gastrointestinal tumors -- as well as melanoma skin cancer and sarcoma, which arise in the bones or soft tissue like muscle or body fat.

But they also had some things in common: Their cancer had spread beyond its original tissue, sometimes to distant sites in the body. And they all had tumors marked by TRK fusions.

The abnormality is a "rare event," Hyman said.

TRK fusions occur in only about 0.5 percent to 1 percent of common cancers, such as colon, breast and lung cancers. But Hyman said they are very common in certain rare cancers such as salivary gland cancer, a form of breast cancer that affects children, and a type of sarcoma in babies.

The abnormality arises when a TRK gene in a cancer cell joins with one of many potential "partner" genes. (Scientists have found more than 50 so far). That, Hyman explained, results in TRK fusion proteins that are constantly "turned on," signaling the cancer cells to keep growing and dividing.

Larotrectinib, an oral medication, is designed to block that TRK activity wherever it occurs.

The new study involved 55 patients, including 12 children. So far, 50 have been on the drug long enough to track their progress.

Overall, Hyman said, about three-quarters have responded to treatment -- meaning their cancer regressed by at least 30 percent. Of those patients, eight in 10 were still on the drug and responding at the one-year mark.

At this point, Hyman said, the longest treatment response has been 25 months and counting.

The most common side effects are fatigue and dizziness. "Patients do very well on it," Hyman said. "You can have a good quality of life while you're taking it."

Last year, the FDA granted larotrectinib "breakthrough therapy" status. That helps speed the development and review process of promising new treatments for serious diseases.

Hyman said he couldn't estimate how long an FDA approval could take.

If the drug is approved, then the question will be: Who should get tested for TRK fusions?

According to Hyman, patients with advanced-stage cancer would have the "greatest need." And even though TRK fusions are uncommon, he thinks testing would be appropriate regardless of the cancer type.

Oh agreed. "TRK fusions are very rare, but in those patients who have them, the consequences with this drug appear to be very significant."

Plus, Oh said, cancer patients are already being tested for other molecular abnormalities to see if they can benefit from targeted drugs. That testing is becoming technically easier and cheaper, he noted.

Dr. Sumanta Kumar Pal is a medical oncologist at City of Hope in Duarte, Calif., and chair of ASCO's Cancer Communications Committee.

He said larotrectinib has the chance to be a "bit of game-changer. There are two important points: This drug may be active irrespective of the cancer site, and irrespective of age."

And while the safety results were encouraging, "it's difficult to draw conclusions based on such a small group of patients," he added.

If the drug is approved by the FDA, Pal said it would make sense to "test early" for TRK fusions in patients with the rare cancers. But with many common cancers, "we'd probably stick with standard care, and then (test) only if that fails," he said.

The study was funded by Loxo Oncology, Inc., which is developing larotrectinib. Hyman and some of his colleagues have received funding from or served as consultants to the company.

Hyman was scheduled to present the findings Saturday at the American Society of Clinical Oncology's annual meeting, in Chicago. Study results presented at meetings are usually considered preliminary until they're published in a peer-reviewed medical journal.

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Experimental Gene-Targeted Drug Hits Cancer Where It Lives - Montana Standard

MONDAY, June 5, 2017 (HealthDay News) -- Two drugs that target genetic flaws are giving people with specific types of advanced lung cancer a chance to live longer and better, a pair of new clinical trials finds.

A newly approved drug called alectinib (Alecensa) works twice as long as the current standard medication in halting cancer growth in patients with ALK-positive non-small cell lung cancer, results from a new global clinical trial show.

ALK is a gene that produces a protein that helps cancer cells grow and spread, according to the American Cancer Society (ACS).

In another study, an experimental drug called dacomitinib delayed cancer growth by about half in non-small cell lung cancer patients who had a mutation of the epidermal growth factor receptor (EGFR) that caused cancer cells to grow faster, a second trial reported. Non-small cell lung cancers comprise most lung cancer cases.

EGFR is a substance normally found on cells that helps them grow and divide, the ACS says.

The drugs, alectinib in particular, will let people live months or years longer just by taking a daily pill, said Dr. Bruce Johnson, chief clinical research officer at Dana-Farber Cancer Institute in Boston. Johnson is also incoming president of the American Society of Clinical Oncology (ASCO).

Alectinib works more than a year longer than crizotinib (Xalkori), which itself supplanted chemotherapy a few years back because it proved more effective with fewer side effects, Johnson said.

"This is kind of a game changer, because the drug itself works at least for two years, plus there are other treatments" that can be substituted when it ultimately becomes ineffective, Johnson said of alectinib. "We used to have to tell these patients 10 or 15 years ago that you've got eight months to a year. Now they most likely have years."

Both of these genetically driven forms of lung cancer are more common in nonsmokers, the ACS says.

The studies were both funded by the drug manufacturers. Hoffmann-La Roche funded the alectinib study. Pfizer and SFJ Pharmaceuticals Group funded the dacomitinib study.

The first clinical trial revealed that alectinib halts lung cancer growth for about 26 months on average. That compared to about 10 months on average for crizotinib, the drug now used as front-line treatment for ALK-positive patients.

Alectinib also works 84 percent better than crizotinib at preventing spread of advanced lung cancer to the brain, because it is better able to penetrate into the brain and kill cancer cells there, said lead researcher Dr. Alice Shaw, director of thoracic oncology at Massachusetts General Hospital Cancer Center in Boston.

About 5 percent of non-small cell lung cancer cases are ALK-positive. That means they have a genetically abnormal protein that fuels cancer growth. In the United States, about 12,500 people are diagnosed with ALK-positive non-small cell lung cancer each year, researchers said in background information.

Alectinib already is approved in the United States as a treatment for ALK-positive patients who no longer respond to crizotinib, Shaw said.

The results should "establish alectinib as the new standard of care" for ALK-positive lung cancer patients, rather than crizotinib, Shaw said.

ASCO expert Dr. John Heymach agreed, calling the clinical trial a "watershed moment."

Not only did the drug work better and longer, but it also produced fewer side effects in patients, noted Heymach, chair of thoracic/head and neck oncology for the University of Texas MD Anderson Cancer Center in Houston.

The most common side effects for alectinib were fatigue, constipation, muscle aches and swelling, while crizotinib patients most often suffered from gastrointestinal problems and liver enzyme abnormalities, according to the researchers.

The second clinical trial compared a new drug, dacomitinib, to the current standard targeted drug gefitinib (Iressa) in treating EGFR-positive lung cancer.

Each year about 15,000 people in the United States are diagnosed with EGFR-positive lung cancer, which involve mutations that increase the growth of cancer cells, researchers said in background notes.

Dacomitinib blocked EGFR mutations more effectively than first-generation drug gefitinib, providing a 41 percent lower chance of cancer progression or death, researchers found. On average, dacomitinib halted cancer growth for 14.7 months in patients, compared with 9.2 months with gefitinib.

"From the perspective of doctors who treat lung cancer daily, this is really a substantial advance," Heymach said, noting that the results put the drug "at the front of the pack in terms of efficacy."

However, dacomitinib also created more side effects, including acne in about 14 percent of patients and diarrhea in 8 percent of patients. Doctors wound up reducing the dosage in about 66 percent of patients as a result of side effects, said lead researcher Dr. Tony Mok, chair of clinical oncology at the Chinese University of Hong Kong.

Heymach said the side effects are "not life-threatening toxicities."

"These are toxicities that doctors who treat this for a living become accustomed to managing," Heymach said.

"At the end of the day, I think we now have one additional choice" in treating EGRF-positive non-small cell lung cancer, Mok concluded, adding that dacomitinib should be considered as a new first-line alternative treatment. The drug has not received FDA approval.

Neither of the tested drugs will be cheap. "Almost all these targeted drugs are thousands of dollars per month," Johnson said.

The results of both trials were scheduled to be presented Monday at ASCO's annual meeting, in Chicago. The findings were also being published June 6 in the New England Journal of Medicine.

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Gene-Targeted Drugs Fight Advanced Lung Cancers - Sioux City Journal

MONDAY, June 5, 2017 (HealthDay News) -- Genetically tuning a person's own immune cells to target cancer appears to provide long-lasting protection against a blood cancer called multiple myeloma, an early trial from China shows.

The treatment, called CAR T-cell therapy, caused 33 out of 35 patients with recurring multiple myeloma to either enter full remission or experience a significant reduction in their cancer.

The results are "impressive," said Dr. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society.

"These are patients who have had prior treatment and had their disease return, and 100 percent of the patients are reported to have had some form of meaningful response to these cells that were administered," Lichtenfeld said.

The new therapy is custom-made for each patient. Doctors collect the patient's own T-cells -- one of the immune system's main cell types -- and genetically reprogram them to target and attack abnormal multiple myeloma cells.

Lead researcher Dr. Wanhong Zhao likened the process to fitting immune cells with a GPS that steers them to cancer cells -- making them into professional killers that never miss their target.

Zhao is associate director of hematology at the Second Affiliated Hospital of Xi'an Jiaotong University in Xi'an, China.

CAR T-cell therapy is promising because the genetically altered T-cells are expected to roost in a person's body, multiplying and providing long-term protection, Lichtenfeld said.

"The theory is they should attack the tumor and continue to grow to become a long-term monitoring and treatment system," Lichtenfeld said. "It's not a one-shot deal."

The technology represents the next step forward in immunotherapy for cancer, said Dr. Michael Sabel, chief of surgical oncology at the University of Michigan.

"Immunotherapy is now really providing hope to a lot of patients with cancers that were not really responding to our standard chemotherapies," Sabel said.

CAR T-cell therapy previously has been used to treat lymphoma and lymphocytic leukemia, Lichtenfeld said.

Zhao and his colleagues decided to try the therapy to treat multiple myeloma. They re-engineered the patients' T-cells and then reintroduced them to the body in three infusions performed within one week.

Multiple myeloma is a cancer that occurs in plasma cells, which are mainly found in bone marrow and produce antibodies to fight infections. About 30,300 people will likely be diagnosed with multiple myeloma this year in the United States, researchers said in background notes.

"Multiple myeloma is a disease that historically was fatal in the course of a couple of years," Lichtenfeld said. During the past two decades, new breakthroughs have extended survival out 10 to 15 years in some patients, he noted.

To date, 19 of the first 35 Chinese patients have been followed for more than four months, researchers report.

Fourteen of those 19 patients have reached the highest level of remission, researchers report. There hasn't been a relapse among any of these patients, including five followed for more than a year.

"That's as far as you can go in terms of driving down the amount of tumor that's in the body," Lichtenfeld said.

Out of the remaining five patients, one experienced a partial response and four a very good response, researchers said.

However, about 85 percent of the patients experienced cytokine release syndrome (CRS), a potentially dangerous side effect of CAR T-cell therapy.

Symptoms of cytokine release syndrome can include fever, low blood pressure, difficulty breathing, and impaired organ function, the researchers said. However, most of the patients experienced only transient symptoms, and "now we have drugs to treat it," Lichtenfeld said.

History suggests the therapy will cost a lot if it receives approval, Lichtenfeld said. However, prior to approval, much more research will be needed, he added.

The Chinese research team plans to enroll a total of 100 patients in this clinical trial at four hospitals in China. They also plan a similar clinical trial in the United States by 2018, Zhao said.

The study was funded by Nanjing Legend Biotech Co., the Chinese firm developing the technology.

The findings were presented Monday at the American Society of Clinical Oncology annual meeting, in Chicago. Data and conclusions presented at meetings are usually considered preliminary until published in a peer-reviewed medical journal.

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Gene-Based Therapy May Thwart a Tough Blood Cancer - Montana Standard

Picture a time in the not-too-distant future when whole genome sequencing is routine. A time when, before babies even learn to talk, their parents will have the ability to learn what the future may have in store for their offspring: Is their little girl predisposed to getting breast cancer? Will their happy-go-lucky son one day develop Alzheimer's?

"There is no doubt in my mind that, in addition to going in and having blood chemistry done, you're gonna have DNA sequencing done, too. It will be there at some point," says Nicholas Schork, a quantitative geneticist at the J. Craig Venter Institute in La Jolla, California, who has studied genomic medicine for more than three decades. "We can debate about the timeline, but it'll become routine."

The hope is that genetic testing will make health care more effective by allowing doctors and patients to focus on areas that need attention the patient's genetic "vulnerabilities." At the same time, patients may learn of areas where they won't need to be quite as vigilant. And treatments could, in turn, be perfectly tailored to a patient's specific needs.

But as with any significant and broadly applicable medical advance, there are questions. For example, should patients learn that they carry markers for currently incurable genetic diseases, or that they are at high risk for developing a condition like Alzheimer's, which has no effective treatment? And just who owns all that genetic data? Who will have access to it?

Even with important questions left unanswered, health educators are moving forward to take advantage of the promises genetic testing offers. Washington State University's new Elson S. Floyd College of Medicine has announced it is partnering with Arivale, a Seattle-based company that conducts whole genome sequencing, to help complete a portrait of a person a "portrait" that can be used to promote wellness over that individual's entire lifespan. Every member of the school's inaugural class will have the opportunity to undergo testing, which will also include blood tests and a lifestyle evaluation. Then, over the next year, Arivale's team of nurses and dietitians will provide individually tailored follow-up, based on each individual's risks and goals. It's a unique partnership, made possible in large part because the medical school is new, with its first class of students starting in 2017.

Allowing the medical students to experience genetic testing firsthand is just part of the goal. "We need physicians that understand it well enough that they can make it better going forward," says John Tomkowiak, founding dean of WSU's College of Medicine. "That's where our students are going to be uniquely positioned."

WHAT GENES TELL US

Genetic testing already provides important information about a person's health or their heritage. Hospitals screen newborn babies for certain genetic disorders, and in some cases, tests can detect disorders before birth. And diagnostic testing can confirm, or rule out, many disorders in adults.

Testing doesn't have to be ordered by a physician. For $200, you can provide a saliva sample, mail it back to 23andMe.com and find out not only your ancestry, but also your risks for a number of diseases, including Alzheimer's and Parkinson's. Ancestry.com offers a glimpse into your heritage for $99. Color.com claims to reveal your risk for the most common hereditary cancers, and even offers "complimentary genetic counseling" for a $249 fee.

But if genetic testing is to revolutionize the health care industry, as many have promised, there's still a ways to go. "The technology is at the beginning stages," says Thomas May, a faculty researcher for the HudsonAlpha Institute for Biotechnology.

Companies like 23andMe offer genetic tests that may provide information about some genetic disorders from currently known genetic variants. But whole genome sequencing is different; it will reveal all your individual genetic variants.

How valuable is that information? There are a relatively small number of conditions that researchers are confident result from a specific genetic variant, May says. For example, there is one variant that researchers have found is associated with an increased risk of developing breast or ovarian cancer. A genetic test that shows an increased risk for breast cancer is considered an "actionable" outcome, meaning there are things you can do to prevent the outcome, like beginning mammograms earlier. Though there are more than 50 actionable outcomes like that, it's still a relatively small number.

Adding to the confusion is the fact that not everyone who develops breast cancer actually has the genetic variant in fact, May says only about 10 percent do. So even if testing shows that you don't have the "breast cancer gene," that doesn't mean it's OK to stop getting mammograms.

"Most variants and correlations are of that type: We can't say for certain if you're gonna get a disease," May says.

Doctors are mixed about whether genetic testing is currently having a real impact on patients. In a May survey conducted by the Medscape Physician Oncology Report on Genomics Testing, 71 percent of oncologists surveyed felt that genetic testing was either "very" or "extremely" important to the oncology field. At the same time, 61 percent said that, currently, fewer than a quarter of their patients would actually benefit from genetic testing.

The number of diseases with "actionable" outcomes will inevitably grow, as more people are tested and more data becomes available. But this leaves deeper questions, says Schork, the quantitative geneticist. A company or health care provider would likely give patients information about diseases that can be prevented or cured. If someone is predisposed to obesity, for instance, then he or she can elect to receive targeted care to reduce that risk.

But what about diseases that, right now, are incurable?

Take Huntington's disease, a genetic disorder that breaks down nerve cells in the brain. It's rare, but it's a "hideous way to die," Schork says. A person can be screened at the age of 25 and be found to carry the Huntington's gene, but there's debate about whether or not that information should be shared with a client or not. The same goes for genetic variants related to Alzheimer's disease.

"If there's nothing they can do about it, then there's a concern about whether or not that information should be imparted," Schork says.

When the Food and Drug Administration ordered 23andMe to stop telling customers their odds of contracting diseases in 2013, Harvard Medical School genetics professor Robert Green and Laura Beskow, a professor at Duke University's Institute for Genome Sciences and Policy, argued against the FDA. They cited a number of studies showing that direct-to-consumer genetic testing does not cause a large percentage of customers despair. In an interview with the New York Times in April, Green said the potential for distress based on results of a genetic test for Alzheimer's was "much smaller than anticipated."

Another question: Who really owns the DNA data that is being collected from willing users of genetic testing? Consider Myriad, a company that offers genetic testing both to help determine cancer risk and design better treatment plans for patients who already have cancer. The company has something that "others do not," Schork says: insight into which genetic variants predispose women to breast cancer.

What Myriad is really selling, then, is not the genetic test itself, but access to insights it has gained through mining its database, insights that can be leveraged into whatever level of payment the company decides to charge.

It's potentially critical information that could help save a life, and some argue that the data should be in the public domain not held by a private company.

"There have been huge debates about whether the community should challenge the monopoly that Myriad has," Schork says. "There are many groups out there that would like to counteract the monopoly Myriad has, by building public domain data sets."

JUST ONE TOOL

"Genetic testing is not a blueprint. It's really not," says Jennifer Lovejoy, chief translational science officer for Arivale. "Genes are really just one factor the environment, diet, exercise, pollutants and even emotional state have a big impact on genes."

That's why Arivale not only collects genetic information on each client, but also evaluates various blood tests and lifestyle factors to create a "dense data cloud" of information about a patient.

"That is the grand vision: that everybody would have these dense, dynamic data clouds, and understand the choices that will be optimal to optimize wellness and avoid disease," says Lovejoy.

Arivale touts the success stories among its nearly 2,000 clients. One client found out he had a gene associated with high sensitivity to saturated fat, giving him a better indication of an appropriate diet that helped him lose weight. Another client discovered that his genes may have an impact on his cholesterol. Another learned he was at risk of developing diabetes.

Ideally, this type of preventive care will soon be covered by insurance, Lovejoy says. The thinking is that preventing disease will bring down the cost of health care overall, making insurers likely to cover more preventive care, "but we have to prove it," Lovejoy says. Researchers are conducting studies and trials to do just that, and if they can prove it, then genetic testing could soon be routine in health care.

"If you think about what health care should mean, it should mean, one, the ability to deal with disease and that's what everyone does today," Arivale co-founder Leroy Hood said at a press conference in April announcing the company's partnership with WSU. "But two, it should mean the ability to optimize wellness for each individual. That is, improving their health and/or letting them avoid disease." That's a concept Hood calls "scientific wellness, and he thinks it could lead to "a whole new health care industry in the future."

Tomkowiak, of WSU's College of Medicine, agrees: "The concept of scientific wellness has the potential to disrupt the entire industry by shifting the cost curve, by keeping people healthier and reducing the cost of health care overall."

Regardless of whether or not Arivale becomes an industry leader, Tomkowiak believes that the practice of medicine will be fundamentally altered in the near future.

"We absolutely believe that seven years from now, the practice of scientific medicine and scientific wellness will be common," he says. "Instead of being behind the curve, we want... to be leading this effort."

For about $3,500, clients can sign up for Arivale's program. The fee includes whole genome sequencing, which is also available from other sources. So how do Arivale clients achieve "scientific wellness"? Here are the elements of their program:

Welcome package: Clients get a welcome package with a Fitbit to track sleep, activity and heart rate. The package asks for information to help understand a client's bacteria in their gut, and asks for a sample of saliva to measure a person's stress level.

Online test: Clients take a series of online assessments about their goals, health history, lifestyle, stress, personality and happiness.

Call from coach: You'll talk to a coach who will get to know what you want to accomplish and give you a personalized action plan.

Labs: You'll take blood tests so your coach can understand your current health. While you're there, they'll take your vital signs.

A picture emerges: The various test create a picture of you, which an Arivale coach will use to provide a step-by-step plan to "optimize your wellness," according to the company.

Follow-up: You're not done yet. You'll be contacted by your coach regularly to review your action plan, and Arivale will provide reports on how you're progressing. Every six months, you'll complete another set of clinical labs.

Source: arivale.com/your-journey

Continued here:
What's In Your Genes? - Pacific Northwest Inlander

SUNDAY, June 4, 2017 (HealthDay News) -- A twice-daily pill could help some advanced breast cancer patients avoid or delay follow-up sessions of chemotherapy, a new clinical trial reports.

The drug olaparib (Lynparza) reduced the chances of cancer progression by about 42 percent in women with breast cancer linked to BRCA1 and BRCA2 gene mutations, according to the study.

Olaparib delayed cancer progression by about three months. The drug also caused tumors to shrink in three out of five patients who received the medication, the researchers reported.

"Clearly the drug was more effective than traditional chemotherapy," said Dr. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society.

"This is a group where a response is more difficult to obtain -- a young group with a more aggressive form of cancer -- and nonetheless we saw a close to 60 percent objective response rate," he said.

The study was funded by AstraZeneca, the maker of Lynparza.

Olaparib works by cutting off the avenues that malignant cancer cells use to stay alive, said lead researcher Dr. Mark Robson. He's a medical oncologist and clinic director of Clinical Genetics Service at Memorial Sloan Kettering Cancer Center in New York City.

The drug inhibits PARP, an enzyme that helps cells repair damaged DNA, Robson said.

Normal cells denied access to PARP will turn to the BRCA genes for help, since they also support the repair of damaged DNA, Robson said.

But that "backup capability" is not available to breast cancer cells in women with BRCA gene mutations, Robson said.

"When you inhibit PARP, the cell can't rescue itself," Robson said. "In theory, you should have a very targeted approach, one specifically directed at the cancers in people who have this particular inherited predisposition."

Olaparib already has been approved by the U.S. Food and Drug Administration for use in women with BRCA-related ovarian cancer. Robson and his colleagues figured that it also should be helpful in treating women with breast cancer linked to this genetic mutation.

The study included 302 patients who had breast cancer that had spread to other areas of their body (metastatic breast cancer). All of the women had an inherited BRCA mutation.

They were randomly assigned to either take olaparib twice a day or receive standard chemotherapy. All of the patients had received as many as two prior rounds of chemotherapy for their breast cancer. Women who had hormone receptor-positive cancer also had been given hormone therapy.

After 14 months of treatment, on average, people taking olaparib had a 42 percent lower risk of having their cancer progress compared with those who received another round of chemotherapy, Robson said.

The average time of cancer progression was about seven months with olaparib compared with 4.2 months with chemotherapy.

Tumors also shrank in about 60 percent of patients given olaparib. That compared with a 29 percent reduction for those on chemotherapy, the researchers said.

Severe side effects also were less common with olaparib. The drug's side effects bothered 37 percent of patients compared with half of those on chemo. The drug's most common side effects were nausea and anemia.

"There were fewer patients who discontinued treatment because of toxicity compared to those who received chemotherapy," Robson said. "Generally it was pretty well tolerated."

Only about 3 percent of breast cancers occur in people with BRCA1 and BRCA2 mutations, the researchers said in background notes.

Despite this, the results are "quite exciting," said Dr. Julie Fasano, an assistant professor of hematology and medical oncology at the Icahn School of Medicine at Mount Sinai in New York City.

Olaparib could wind up being used early in the treatment of metastatic breast cancer as an alternative to chemotherapy, and future studies might find that the drug is effective against other forms of breast cancer, Fasano said.

"It may be a practice-changing study, in terms of being able to postpone IV chemotherapy and its associated side effects" like hair loss and low white blood cell counts, Fasano said.

Lichtenfeld noted that olaparib also places less burden on patients.

"It may be easier for women to take two pills a day rather than go in for regular chemotherapy," Lichtenfeld said. "Clearly, this is a treatment that will garner considerable interest.

The findings were scheduled to be presented Sunday at the American Society of Clinical Oncology's annual meeting, in Chicago. The study was also published June 4 in the New England Journal of Medicine.

More here:
Drug Helps Fight Breast Tumors Tied to 'Cancer Genes' - Sioux City Journal

By Laurie McginleyThe Washington Post

The oncologist was blunt: Stefanie Joho's colon cancer was raging out of control and there was nothing more she could do. Flanked by her parents and sister, the 23-year-old felt something wet on her shoulder. She looked up to see her father weeping.

"I felt dead inside, utterly demoralized, ready to be done," Joho remembers.

But her younger sister couldn't accept that. When the family got back to Joho's apartment in New York's Flatiron district, Jess opened her laptop and began searching frantically for clinical trials, using medical words she'd heard but not fully understood. An hour later, she came into her sister's room and showed her what she'd found.

"I'm not letting you give up," she told Stefanie. "This is not the end."

That search led to a contact at Johns Hopkins University, and a few days later, Joho got a call from a cancer geneticist co-leading a study there.

"Get down here as fast as you can!" Luis Diaz said. "We are having tremendous success with patients like you."

What followed is an illuminating tale of how one woman's intersection with experimental research helped open a new frontier in cancer treatment with approval of a drug that, for the first time, targets a genetic feature in a tumor rather than the disease's location in the body.

The breakthrough, now made official by the Food and Drug Administration, immediately could benefit some patients with certain kinds of advanced cancer that aren't responding to chemotherapy. Each should be tested for that genetic signature, scientists stress.

"These are people facing death sentences," said Hopkins geneticist Bert Vogelstein. "This treatment might keep some of them in remission for a long time."

A pivotal small trial

In August 2014, Joho stumbled into Hopkins for her first infusion of the immunotherapy drug Keytruda. She was in agony from a malignant mass in her midsection, and even with the copious amounts of OxyContin she was swallowing, she needed a new fentanyl patch on her arm every 48 hours. Yet within just days, the excruciating back pain had eased. Then an unfamiliar sensation hunger returned. She burst into tears when she realized what it was.

As months went by, her tumor shrank and ultimately disappeared. She stopped treatment this past August, free from all signs of disease.

The small trial in Baltimore was pivotal, and not only for the young marketing professional. It showed that immunotherapy could attack colon and other cancers thought to be unstoppable. The key was their tumors' genetic defect, known as mismatch repair (MMR) deficiency akin to a missing spell-check on their DNA. As the DNA copies itself, the abnormality prevents any errors from being fixed. In the cancer cells, that means huge numbers of mutations that are good targets for immunotherapy.

The treatment approach isn't a panacea, however. The glitch under scrutiny which can arise spontaneously or be inherited is found in just 4 percent of cancers overall. But bore in on a few specific types, and the scenario changes dramatically. The problem occurs in up to 20 percent of colon cancers and about 40 percent of endometrial malignancies cancer in the lining of the uterus.

In the United States, researchers estimate that initially about 15,000 people with this defect may be helped by this immunotherapy. That number is likely to rise sharply as doctors begin using it earlier on eligible patients.

Joho was among the first.

Even before Joho got sick, cancer had cast a long shadow on her family. Her mother has Lynch syndrome, a hereditary disorder that sharply raises the risk of certain cancers, and since 2003, Priscilla Joho has suffered colon cancer, uterine cancer and squamous cell carcinoma of the skin.

Stefanie's older sister, Vanessa, had already tested positive for Lynch syndrome, and Stefanie planned to get tested when she turned 25. But at 22, several months after she graduated from New York University, she began feeling unusually tired. She blamed the fatigue on her demanding job. Her primary-care physician, aware of her mother's medical history, ordered a colonoscopy.

When Joho woke up from the procedure, the gastroenterologist looked "like a ghost," she said. A subsequent CT scan revealed a very large tumor in her colon. She'd definitely inherited Lynch syndrome.

She underwent surgery in January 2013 at Philadelphia's Fox Chase Cancer Center, where her mother had been treated. The news was good: The cancer didn't appear to have spread, so she could skip chemotherapy and follow up with scans every three months.

By August of that year, though, Joho started having relentless back pain. Tests detected the invasive tumor in her abdomen. Another operation, and now she started chemo. Once again, in spring 2014, the cancer roared back. Her doctors in New York, where she now was living, switched to a more aggressive chemo regimen.

"This thing is going to kill me," Joho remembered thinking. "It was eating me alive."

Genetics meets immunology

Joho began planning to move to her parents' home in suburban Philadelphia: "I thought, 'I'm dying, and I'd like to breathe fresh air and be around the green and the trees.' "

Her younger sister wasn't ready for her to give up. Jess searched for clinical trials, typing in "immunotherapy" and other terms she'd heard the doctors use. Up popped a trial at Hopkins, where doctors were testing a drug called pembrolizumab.

"Pembro" is part of a class of new medications called checkpoint inhibitors that disable the brakes that keep the immune system from attacking tumors. In September 2014, the treatment was approved by the FDA for advanced melanoma and marketed as Keytruda. The medication made headlines in 2015 when it helped treat former President Jimmy Carter for melanoma that had spread to his brain and liver. It later was cleared for several other malignancies.

Yet researchers still don't know why immunotherapy, once hailed as a game changer, works in only a minority of patients. Figuring that out is important for clinical as well as financial reasons. Keytruda, for example, costs about $150,000 a year.

By the time Joho arrived at Hopkins, the trial had been underway for a year. While an earlier study had shown a similar immunotherapy drug to be effective for a significant proportion of patients with advanced melanoma or lung or kidney cancer, checkpoint inhibitors weren't making headway with colon cancer. A single patient out of 20 had responded in a couple of trials.

Why did some tumors shrink while others didn't? What was different about the single colon cancer patient who benefited? Drew Pardoll, director of the Bloomberg-Kimmel Institute for Cancer Immunotherapy at Hopkins, and top researcher Suzanne Topalian took the unusual step of consulting with the cancer geneticists who worked one floor up.

"This was the first date in what became the marriage of cancer genetics and cancer immunology," Pardoll said.

In a brainstorming session, the geneticists were quick to offer their theories. They suggested that the melanoma and lung cancer patients had done best because those cancers have lots of mutations, a consequence of exposure to sunlight and cigarette smoke. The mutations produce proteins recognized by the immune system as foreign and ripe for attack, and the drug boosts the system's response.

And that one colon-cancer patient? As Vogelstein recalls, "We all said in unison, 'He must have MMR deficiency!' " because such a genetic glitch would spawn even more mutations.

When the patient's tumor tissue was tested, it was indeed positive for the defect.

The researchers decided to run a small trial, led by Hopkins immunologist Dung Le and geneticist Diaz, to determine whether the defect could predict a patient's response to immunotherapy. The pharmaceutical company Merck provided its still-experimental drug pembrolizumab. Three groups of volunteers were recruited: 10 colon cancer patients whose tumors had the genetic problem; 18 colon cancer patients without it; and 7 patients with other malignancies with the defect.

The first results, published in 2015 in the New England Journal of Medicine, were striking. Four out of the 10 colon cancer patients with the defect and 5 out of the other 7 cancer patients with the abnormality responded to the drug. In the remaining group, nothing. Since then, updated numbers have reinforced that a high proportion of patients with the genetic feature benefit from the drug, often for a lengthy period. Other trials by pharmaceutical companies have shown similar results.

The Hopkins investigators found that tumors with the defect had, on average, 1,700 mutations, compared with only 70 for tumors without the problem. That confirmed the theory that high numbers of mutations make it more likely the immune system will recognize and attack cancer if it gets assistance from immunotherapy.

For Joho, now 27 and living in suburban Philadelphia, the hard lesson from the past few years is clear: The cancer field is changing so rapidly that patients can't rely on their doctors to find them the best treatments.

"Oncologists can barely keep up," she said. "My sister found a trial I was a perfect candidate for, and my doctors didn't even know it existed."

Her first several weeks on the trial were rough, and she still has some lasting side effects today joint pain in her knees, minor nausea and fatigue.

"I have had to adapt to some new limits," she acknowledged. "But I still feel better than I have in five years."

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IT'S A START: Newly approved gene therapy may help 4 percent of cancer patients - Sarasota Herald-Tribune