Study characteristics

Sixteen studies were included in the analysis [46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61]. Most were quantitative (n=12), using questionnaires to assess public perceptions [46,47,48,49,50,51,52, 54, 56, 57, 59, 61]. Three studies conducted focus groups [53, 55, 60] while one study used both focus groups and a survey [58]. The US has contributed the most to this field thus far, undertaking six of the 16 studies identified in the literature search [49, 50, 52, 53, 55, 58]. This is followed by Canada (n=2) [48, 51] and Japan (n=2) [54, 59]. Each of the following countries contributed one study: Jordan [56], Korea [57], The Netherlands [61], Singapore [60], Qatar [46] and the UK [47]. Ten of the studies attempted to recruit a representative sample [46,47,48,49, 51, 53, 54, 56, 59, 61]. Higher educated participant populations (compared to the general population) were noted in four studies [48, 59,60,61]. Three studies recruited participants from specific sites [52, 55, 57]. No studies attempted to discern the views of underrepresented populations aside Mallow et al. [58] who conducted focus groups with a rural community (Table3, Supplementary File3).

Education level influenced decisions to hypothetically partake in genomic testing in different ways [49, 51, 56, 59, 61]. Three studies found that more educated individuals were more likely to be interested in testing [49, 56, 59], while two other studies found that being more educated led to more critical attitudes towards testing [51, 61]. One study found no association between education level and attitude towards testing [57]. Khadir, Al-Qerem and Jarrar [56] found that having a low perceived knowledge of genomic testings social consequences reduced the likelihood of having a reserved attitude. Abdul Rahim et al. [46] found genetic/genomic knowledge did not impact whether a participant would engage in testing.

The age of the participant was reported to influence decision making [49, 54, 56, 57, 59], with no consensus on attitudes of older versus younger adults. Lee et al. [57] found that older adults were more likely to approve of integrating personalised medicine testing into standard healthcare. Two other studies also found that older adults were slightly more interested in genomic testing [54, 56]. In contrast, Okita et al. [59] found that older adults were less willing to partake in genomic testing, while Dodson et al. [49] found no association between age and likeliness to have testing.

Abdul Rahim et al. [46] found that marital status was not significantly associated with willingness to partake in testing in Qatari adults, while Dodson et al. [49] found American participants planning to have children in the next five years had significantly increased interest in testing. Dodson et al. [49] was the only study to investigate whether ethnicity influenced decision-making, showing no association.

Okita et al. [59] assessed the influence of employment status on willingness to partake, reporting that students had significantly more positive attitudes towards testing compared to employed respondents. Bombard et al. [48] found that having an income of more than CAD$80,000 led to a 11-12% decrease in likeliness of believing parents have a responsibility to have their child tested via expanded NBS. No study assessed the impact of sex on attitude towards testing, however Lee et al. [57] found that sex did not significantly influence whether the participant had heard of personalised medicine.

Using the NASSS domains we were able to map primary source data to technology (Domain 2), value proposition (Domain 3), the adopter system (Domain 4) and the wider context (Domain 6) (Fig.2). Greenhalgh et al. [39] does not provide specific definitions for their domains, rather they frame these domains in the form of questions that need to be answered. We replicated this approach and adapted the questions to align with our study questions (Supplementary File4).

The NASSS Framework considers the influences on adoption, nonadoption, abandonment, spread, scale-up, and sustainability of healthcare technologies. Domains 2 (Technology), 3 (Value proposition), 4 (Adopter system) and 6 (Wider context) of the NASSS Framework have been addressed in this scoping review to consider how public perceptions are incorporated in the framework.

Domain 2 considers the technical aspects of the technology that will influence its implementation [39]. Questions 2B, types of data generated; 2C, knowledge needed to use the technology; and 2E, Who owns the IP generated by the technology?, are addressed in the primary sources.

This question considers the knowledge generated by the technology and how this is perceived by patients and/or caregivers. Two studies cited the accuracy of genetic information as an issue for their participants [54, 58].

Greenhalgh et al. [39] defines this as the type of knowledge needed by both healthcare providers and patients to use the technology. However, we will only focus on the views of the general public. Although patients of genomic testing do not necessarily need knowledge to undertake testing, the informed consent process is essential. To gain informed consent from patients, understanding the baseline genomic knowledge of the public is beneficial for those taking consent. Knowledge of genetics and genomics was assessed in several different ways across the included articles [46, 52,53,54, 56, 58, 60]. These included asking participants if they had heard of various genetic and/or genomic terms, how they had heard about genomic testing, how participants describe genomics (in a focus group setting) and questions on genetics knowledge.

Abdul Rahim et al. [46] found that less than a third (n=245) of survey respondents had heard of genomic testing while just over half (n=447) had heard of genetic testing. Gibson, Hohmeier and Smith [52] found that 54% (n=7) of their participants had heard the term pharmacogenomics. Hishiyama, Minari and Suganuma [54] found that more than two-thirds of their participants had heard of classic genetic terminology (e.g. DNA, gene, chromosome), whereas fewer participants had heard of newer, genomics terminology (e.g. personal genome and pharmacogenomics). Hahn et al. [53] found that the majority of their participants had not heard the term genomic medicine and personalised medicine. Ong et al. [60] found that English and Mandarin-speaking participants had heard of the term personalised medicine but not precision medicine, while Malay-speaking participants had not heard of either term.

Three studies questioned participants on how they had heard about genomics [46, 52, 53]. Abdul Rahim et al. [46] asked about both genetic and genomic testing whereas Gibson, Hohmeier and Smith [52] asked their participants where they had heard certain terms from. Abdul Rahim et al. [46] found that 30% (n=69) of participants who knew of genomic testing, heard about it through word of mouth. Gibson, Hohmeier and Smith [52] found that 54% (n=7) of participants had heard of pharmacogenomic testing, and other key terms associated with genomics, from the internet. Hahn et al. [53] used focus groups to discern participant understanding of the term genomic medicine, and found that some college students had heard of the term on the news and in biology classes.

Two studies used focus groups to discern genomic understanding [53, 58]. Mallow et al. [58] used a Community Participating Research approach. Community leaders suggested they use terms like genes and family health history rather than scientific terminology to assist discussions with the community. They found that participants were more likely to describe inheriting disease rather than inheriting health and wellness [58]. Hahn et al. [53] found that their focus group participants described genomic medicine in terms of genetics, family history, the genome project, using genetics to heal people and cloning. Ong et al. [60] also used focus groups to discuss baseline understanding of personalised medicine and precision medicine divided into the primary language spoken by the participants, allowing for discussions on terminology specific to the language.

Knowledge of genetic and/or genomic facts was directly assessed in two studies [46, 56]. Abdul Rahim et al. [46] and Khadir, Al-Qerem and Jarrar [56] both questioned respondents on their basic genetic literacy via survey questions. Abdul Rahim et al. [46] found that 56.1% of survey respondents (n=464) were able to answer at least 5 out of 8 genetic literacy questions correctly, while Khadir, Al-Qerem and Jarrar [56] found that participants were knowledgeable in hereditary genetic information but not other scientific facts. Khadir, Al-Qerem and Jarrar [56] also gave participants the opportunity to self-report their knowledge of genetics. Many participants reported having sufficient knowledge on basic medical uses of testing and potential social consequences, such as refusing testing and the rights of third parties to request genetic test results of individuals [56].

For genomic testing, we have interpreted this question to mean whether patients own their genetic information or if it belongs to the group that conducts sequencing. Four studies found that participants had concerns about the privacy of their or their childs genetic information [46, 53, 55, 57]. Hishiyama, Minari and Suganuma [54] also found that 37.1% (n=1112) of their participants were concerned about management and storage of genetic information.

Greenhalgh et al. [39] use this domain to consider the value placed on the technology by healthcare professionals and the patient. Question 3B, demand-side value (to patient), is addressed in the primary sources.

Greenhalgh et al. [39] define this question as the downstream value of the technology, including the evidence of benefit to patients and affordability. Willingness to pay for genomic testing was directly assessed in three studies [50, 52, 57]. Gibson, Hohmeier and Smith [52] found that if the entire cost of the pharmacogenomic test was covered by insurance, 89% of participants (n=24) would undertake testing [52]. Lee et al. [57] determined that age, gender, income, inconvenience of testing and prior knowledge all influenced whether participants would pay extra for personalised medical testing. Cost of testing was a concern for 44.8% of participants (n=316) [57]. Edgar et al. [50] found that most adoptees (72.4%) and non-adoptees (80.3%) were willing to pay between US$1 and US$499. Education level was a predictor for adoptee willingness to pay, while income predicted willingness to pay in non-adoptees [50]. Abdul Rahim et al. [46] did not directly assess willingness to pay, however they noted that a high income was associated with participant willingness to partake in testing.

Hahn et al. [53] and Ong et al. [60] did not directly assess willingness to pay for genomic sequencing, but participants did express concerns about the cost of testing to the individual and whether there would be equitable access to testing.

Greenhalgh et al. [39] use this domain to consider the adoption of the technology. The adopter system includes caregivers, healthcare professionals and patients. Question 4B addresses whether patients will adopt a technology, while 4C addresses if lay caregivers are available to facilitate adoption. As we did not include patients or lay caregivers in our review, we have adapted these definitions to incorporate hypothetical patients and/or carers under the term genomic naive public. Greenhalgh et al. [39] also emphasise patient acceptance and family conflict as influencing factors on use of technology.

Several personal values were identified across the included studies [46, 48,49,50,51,52,53,54, 56, 59]. Abdul Rahim et al. [46] and Hishiyama, Minari and Suganuma [54] found that contributing to science and medical research were reasons to partake [46, 54]. Other reasons for partaking in genomic testing suggested by Qatari adults included improved health knowledge and prevention of future health conditions [46]. This was also suggested by participants in Etchegary et al. [51], Hahn et al. [53] Khadir, Al-Qerem and Jarrar [56].

Bombard et al. [48] found that most of their participants preferred using scientific evidence (82%, n=994) and receiving expert advice (74%, n=897) when making important healthcare decisions. However, only half (53%) of participants had trust in healthcare (n=639). Hahn et al. [53] also found that many participants were sceptical of genomic medicine specifically, and often associated it with genetic engineering and cloning despite these not being directly related to genomic testing. Some participants felt they did not need the information genomic testing could provide, while others who would hypothetically want testing, believed it could promote the development of new treatments and provide more information on family history [53].

Primary reasons for not willing to partake in testing, as noted by Abdul Rahim et al. [46] were lack of time, information or knowledge, and privacy concerns. Similar concerns were suggested by Hahn et al. [53] and Lee et al. [57]. Fear of the unknown was also suggested in Hahn et al. [53] and Mallow et al. [58]. Participants in Hahn et al. [53] also noted they may be uncomfortable with the results, and the results may be too deterministic.

Aside from general concerns about the nature of genomic testing, concern regarding communication of genetic information among family members was also highlighted [47, 51, 53, 56, 58, 61]. Ballard et al. [47] noted that most participants, whether asked to imagine either they or a family member had a genetic condition, believed other family members who might also be affected should be notified. Etchegary et al. [51] and Khadir, Al-Qerem and Jarrar [56] also found that most participants would share genomic test results with family members. Participants in Hahn et al. [53] generally had a positive view of learning about genetic information if it would help other family members as some had family members who had passed away without explanation. Mallow et al. [58], however, found that communicating genetic information to family members may be an issue. Participants cited several reasons for this including: upsetting children and the creation of family issues, older family members not willing to disclose information and stigmatisation by the community, particularly if the information in question regarded mental illness or substance abuse disorders [58]. Participants also suggested they would only discuss genetic risk if there was a health crisis in the family [58]. Etchegary et al. [51], although noting that many participants would want to share information, found that those with the highest education levels and income were less likely to share results with family members. Vermeulen et al. [61] also found that 17% of their participants (n=160) were worried about causing friction within their families. However, participants who believed family history assessments were worthwhile cited disease prevention as a benefit to involving family members [61].

Greenhalgh et al. [39] describe the wider context as the institutional and sociocultural contexts. Examples of the wider context include health policy, fiscal policy, statements and positions of professional and peak bodies, as well as law and regulation. Here, in order to respond to our research questions, we focus on the socio-cultural aspects of the public.

Societal concerns were noted in many studies [51, 53,54,55,56, 58, 60, 61]. Twenty-two percent of participants (n=1425) in the Hishiyama, Minari and Suganuma [54] study noted employment and insurance discrimination as a concern. This was also noted in Etchegary et al. [51] and Khadir, Al-Qerem and Jarrar [56]. Participants in Hahn et al. [53] and Mallow et al. [58] noted discrimination and segregation as key societal issues that may arise. One-third of participants (n=311) in Vermeulen et al. [61] thought that individuals may be coerced into testing if it is normalised.

Cultural context may influence participant responses. For example, Abdul-Rahim et al. found the 45.1% of their respondents (n=241) were in consanguineous relationships [46]. No other study reported on consanguinity, demonstrating that different cultures prioritise different elements when reporting. Abdul-Rahim et al. found that 70.9% population (n=584) were willing to undergo genomic testing [46], whereas Dodson et al. found that 39.5% of their US population (n=805) were somewhat interested and 19.1% (n=389) were definitely interested in genomic testing [49]. These papers demonstrates that different cultures can influence perceptions of genomic testing. However, the Caucasian US population in Gibson et al. were more willing to undergo testing at 81.0% (n=21) [52], showing that even within the same country there can be cultural differences that may lead to differences in perception.

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How does the genomic naive public perceive whole genomic testing for health purposes? A scoping review | European Journal of Human Genetics -...

DUBLIN--(BUSINESS WIRE)--The "Global Genetic Testing Market Research and Forecast, 2022-2028" report has been added to ResearchAndMarkets.com's offering.

The global genetic testing market is growing at a significant CAGR during the forecast period. The genetic disorder can be occurred by a change in one gene (monogenic disorder), by changes in multiple genes by a combination of environmental factors, and gene mutations, or by the destruction of chromosomes. Genetic testing is a medical test that is used for the identification of mutations in genes or chromosomes.

The key benefit of genetic testing is the chance to know the risk for a certain disease that possibly can be prevented, identify the disease or a type of disease, identify the cause of a disease, to determine options for a disease. The disease that can be identified by genetic testing includes, breast and ovarian cancer, Age-Related Macular Degeneration (AMD), bipolar disorder, Parkinson's disease, celiac disease, and psoriasis.

The global genetic testing market is projected to considerably grow in the upcoming year due to the prevalence of genetic disorders, cancer, and chronic disease. Moreover, continuous advancement by the medical companies in the genetic diagnostic field is also augmenting the market growth.

These companies are finding new and better tests for the accurate diagnosis of the most prevalent as well as rare diseases. Besides, the increase in awareness between people about health and the increased mortality rate due to genetic diseases across the globe is also a major factor increasing the need for demand for genetic testing.

Moreover, The adoption of (DTC) direct-to-consumer genetic testing kits in countries such as the US, China, and Japan, is increasing rapidly. With growing technological acceptances, awareness programs, and a drop in costs, the market for DTC-GT kits is likely to witness a significant boost over the forecast period. However, the lack of diagnostic infrastructure in emerging economies is a challenging factor for market growth.

Regional Outlooks

North America is estimated to contribute a significant share in the global genetic testing market due to the high awareness among the people about advanced treatment for healthcare, well-developed healthcare infrastructure, presence of key players, and availability of drugs.

Moreover, an increase in government initiatives for the enhancement of healthcare facilities and funding in research in the region is also a major factor for the significant market share of the region. In the US under the US CDC EGAPP, inventiveness has been taken by the government such as the Evaluation of Genomic Applications in Practice and Prevention which is also motivating the market growth.

One of the key goals of the initiative is to timely, offer objectively, and credible information that is linked to available scientific evidence. These statistics will allow healthcare workers and payers, customers, policymakers, and others to differentiate genetic tests that are safe and useful.

Asia-Pacific will have considerable growth in the global Genetic Testing Market

In Asia Pacific, the market is increasing due to government initiatives in research and the increasing prevalence of chronic diseases. Apart from cancer, genetic testing processes have also come in easy reach for the diagnosis of inherited cardiovascular diseases such as cardiac amyloidosis, Brugada syndrome, and familial dilated cardiomyopathy. As the region has a high incidence of cardiovascular diseases, significant scope for genetic testing can be witnessed in the region during the forecast period.

Market Players Outlook

The report covers the analysis of various players operating in the global genetic testing market. Some of the major players covered in the report include Abbott Laboratories, Myriad Genetics, Inc., F. Hoffmann-La Roche Ltd., Illumina, Inc., and Thermo Fisher Scientific, Inc. To survive in the market, these players adopt different marketing strategies such as mergers and acquisitions, product launches, and geographical expansion.

The Report Covers

Market Segmentation

Global Genetic Testing Market by Technology

Global Genetic Testing Market by Type

Global Genetic Testing Market by Disease

Company Profiles

For more information about this report visit https://www.researchandmarkets.com/r/fvmuud

About ResearchAndMarkets.com

ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.

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Global Genetic Testing Market Research Report 2022 Featuring Major Players - Abbott Laboratories, Myriad Genetics, F. Hoffmann-La Roche, Illumina, and...

The outcomes from biologics and cell therapies hinge on what they secrete. More specifically, protein secretion has important impacts for both the quality and quantity of a therapeutic produced using bioprocessing, says Dino Di Carlo, PhD, the Armond and Elena Hairapetian chair in engineering and medicine at the University of California, Los Angeles.

For biologics, he continues, the rate at which producer cells secrete protein therapeuticsfor example, monoclonal antibodiesdrives the amount of therapeutic that can be produced per batch and ultimate costs of production; for cell therapies, secreted proteins are a key product attribute that defines a high-quality product.

A previous GEN story explained how secretion-based screening could improve cell therapies. Here, Di Carlo describes how he and his colleagues used single-cell sequencing information (SEC-seq) to link the secretions and transcriptomes for individual antibody-secreting cells.

The key finding from this work, Di Carlo says, is that gene transcripts are not necessarily correlated to secreted proteins, which makes the community rethink genetic modificationapproaches that just focus on overexpressing the gene for the target-secreted protein to achieve animproved therapeutic effect. For example, the SEC-seq study showed that the levels of mRNA transcripts for immunoglobulin G (IgG) proteins did not correlate with the amount of assembled and secreted IgGheavy and light chainin humanplasma cells.

Instead, in highly secreting cells, we found pathways upregulated that drive energy production, protein translation, protein trafficking, and response to misfolded proteins, Di Carlo explains. This suggests that having enough transcripts around to produce the secreted protein is not the bottleneck for high levels of secretion. As he adds, Other pathways are the likelybottleneck, and they are needed to make and traffic a lot of protein to the membrane to secrete it, as well as deal with mis-folded proteins that result from translation of large quantities of proteins.

Upon understanding the importance of secretions from biologics and cell-based therapies, what can a commercial bioprocessor do about it? One implication is for bioprocessors interested in the genetic modification of therapeutic cells to secrete more of a therapeutic protein, Di Carlo says. Our results suggest it is not sufficient to genetically modify your cell type of interest with just the gene to produce a secreted protein, because you may also need to drive these other associated pathways to enhance the level of secretion.

The SEC-seq method could also be applied in other ways. Bioprocessors could use this technique to identify the pathways that drive secretion of critical cytokines and growth factors for their therapeutic cell type of interest, Di Carlo says. For example, there may be differences in what drives high levels of secretion between the human plasma cells secreting IgG and natural killer cells secreting cytokines. This information could be used by a bioprocessor to improve the base cell types used for a therapeutic product or to perform quality control or production-batch sorting based on these factors.

For biologics, bioprocessors can use SEC-seq to uncover what drives higher secretion of a therapeutic protein by producer cell types, like CHO cells, HEK293 cells, etc., Di Carlo explains. The information obtained could help engineer the next generation of more efficient and productive producer cell lines.

So, making an effective biologic or cell therapy depends on what cells secrete. Fortunately, Di Carlos work will help bioprocessors better understand and improve that secretion.

Continued here:
Tracking Transcripts in Biologics and Cell Therapies - Genetic Engineering & Biotechnology News

NEW YORK & CAMBRIDGE, England--(BUSINESS WIRE)--Empyrean Neuroscience, Inc., a leading genetic engineering company dedicated to developing neuroactive compounds to treat neuropsychiatric and neurologic disorders, today announced that it has launched with a $22 million Series A financing and a genetic engineering platform to advance a pipeline of neuroactive compounds targeting disorders of the central nervous system (CNS). The company is founded on a proprietary platform designed to genetically engineer small molecule therapeutics from fungi and plants. Veteran biotech executives Usman Oz Azam, M.D., Chief Executive Officer, and Fred Grossman, D.O., FAPA, Chief Medical Officer, lead the company.

Through precision targeting and engineering of the fungal and plant genomes, Empyrean is working to enhance and modulate neuroactive compounds produced by these kingdoms. The platform is being used to identify therapeutic fungal alkaloids, cannabinoids, and other small molecules that may exhibit enhanced efficacy and safety. In addition, the platform is designed to discover novel small molecules that may exhibit a therapeutic benefit.

There is an enormous medical need for safe and effective therapeutics that treat neuropsychiatric and neurologic disorders and we believe genetic engineering provides the answer, said Dr. Azam, Empyreans Chief Executive Officer. By applying our genetic engineering platform to make precise modifications to the genomes of fungi and plants, we can change the amount and kind of neuroactive small molecules they produce, with the goal of developing safe and effective treatments for difficult-to-treat diseases of the CNS.

The companys developmental pipeline includes fungal alkaloids, cannabinoids, and other neuroactive compounds, such as N,N-Dimethyltryptamine (DMT), for the potential treatment of major depressive disorder (MDD), post-traumatic stress disorder (PTSD), neurologic disorders, substance abuse and dependence, and chronic pain. Investigational New Drug (IND) enabling studies of the companys first genetically engineered encapsulated mushroom drug product are currently underway, and the company aims to enter the clinic for MDD in 2023.

Fungal alkaloids and cannabinoids have shown promise in treating depression, PTSD, anxiety, and other neuropsychiatric and neurologic disorders, said Dr. Grossman, Empyreans Chief Medical Officer. We believe our approach of genetically engineering fungi and plants can improve their safety and efficacy and will ultimately help to address the substantial unmet medical need in patients who suffer from these diseases.

As part of its genetic engineering platform, the company has licensed CRISPR/Cas9 technology from ERS Genomics for genetic engineering applications related to its therapeutic pipeline.

Dr. Azam was previously President and Chief Executive Officer of Tmunity Therapeutics, a biotech developing genetically engineered cell therapies for applications in cancer. Before Tmunity, he was Global Head of Cell & Gene Therapies at Novartis, where he was responsible for commercial operations, business development licensing, new product commercialization, clinical development, regulatory affairs, and other aspects of the global cell and gene therapies business. He was Chief Executive Officer of Novaccel Therapeutics, Chief Medical Officer of Aspreva Pharmaceuticals, and earlier in his career, held positions at Johnson & Johnson, GSK, and Pfizer. Dr. Azam received his M.D. from the University of Liverpool School of Medicine and is board certified in obstetrics and gynecology in the United Kingdom.

Before joining Empyrean, Dr. Grossman was Chief Medical Officer of Mesoblast Ltd. and President and Chief Medical Officer of Glenmark Pharmaceuticals. He has held executive leadership positions in large pharmaceutical companies, including Eli Lilly, Johnson & Johnson, Bristol Myers Squibb, and Sunovion. He has been responsible for leading the development, approval, and supporting the launch of numerous global medications addressing significant unmet medical needs across therapeutic areas, particularly in the CNS. He has held academic appointments and has authored numerous scientific publications. He was trained in psychiatry at Hahnemann University in Philadelphia and at the National Institute of Mental Health in Bethesda, Maryland and completed a Fellowship in the Section on Clinical Pharmacology at the National Institutes of Health. Dr. Grossman is a board-certified psychiatrist and Fellow of the American Psychiatric Association.

About Empyrean Neuroscience

Empyrean Neuroscience is a genetic engineering company developing a pipeline of neuroactive therapeutics to treat a range of neuropsychiatric and neurologic disorders. Through precision genetic modification, transformation, and regeneration of fungi and plants, the platform allows for the creation of small molecule therapeutics. In addition, the platform enables the discovery of novel small molecules that may exhibit therapeutic properties. The company is based in New York City and Cambridge, UK.

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Empyrean Neuroscience Launches with $22M Series A and Genetic Engineering Platform to Advance Pipeline of Neuroactive Compounds Targeting CNS...

Depression Treatment: How Genetic Testing Can Help Find the Right Medication

Depression Treatment: How Genetic Testing Can Help Find the Right Medication

17 October,2022 08:42 am

ISLAMABAD, (Online) - Thats according to a new studyTrusted Source conducted by the U.S. Department of Veterans Affairs (VA) and published today in the Journal of the American Medical Association.

In it, researchers report that pharmacogenetic testing might help medical professionals by providing helpful information on how a person metabolizes a medication. This information can help doctors and others avoid prescribing antidepressants that could produce undesirable outcomes.

Depression medication is sometimes determined through trial and error to find the best drug and dosage. The researchers say they hope genetic testing can minimize this by giving insight into how a person may metabolize a drug.

Researchers said genetic testing did not show how a person would react to a particular medication but instead looked at how a person metabolized a drug. A drug-gene interaction is an association between a drug and a generic variation that may impact a persons response to that drug. Learning more about drug-gene interactions could potentially provide information on whether to prescribe medication and whether a dosage adjustment is needed.

In the study, around 2,000 people from 22 VA medical centers diagnosed with clinical depression received medications to treat their symptoms. The participants were randomized, with one-half receiving usual care and one-half undergoing pharmacogenetic testing.

For those that received usual care, doctors prescribed medication without the benefit of seeing a genetic testing result. The researchers found that 59 percent of the patients whose doctors received the genetic testing results used medications with no drug-gene interaction. Only 26 percent of the control group received drugs with no drug-gene interaction.

The researchers said the findings show that doctors avoided medications with a predicted drug-gene interaction.

Most often, patients get tested after at least one or two drugs havent worked or they had severe side effects, said Dr. David A. Merrill, a psychiatrist and director of the Pacific Neuroscience Institutes Pacific Brain Health Center at Providence Saint Johns Health Center in California. There are real genetically driven differences in how people metabolize drugs. It helps select more tolerable options to know about their genetics ahead of time.

Researchers interviewed participants about their depression symptoms at 12 weeks and 24 weeks.

Through 12 weeks, the participants who had genetic testing were more likely to have depression remission than those in the control group.

At 24 weeks, the outcome was not as pronounced. The researchers said this showed that genetic testing could relieve depressive symptoms faster than if a person did not receive the testing.

What experts think

There is a place for pharmacogenetic testing when treating people with depression, according to Dr; Alex Dimitriu, an expert in psychiatry and sleep medicine and founder of Menlo Park Psychiatry & Sleep Medicine in California and BrainfoodMD.

Some situations that might call for genetic testing include treatment-resistant depression and more complex cases.

It tells me if someone will either rapidly or slowly metabolize a drug meaning the level of the drug will either be too low or too high depending on the persons metabolism, Dimitriu told Healthline. I have used it in a few rare cases to see what options remain.

To me, more important than pharmacogenetic testing is watching the symptoms and response in my patients, he continued. I see my patients often, especially when starting a new medicine, and we can go slow and watch how the patient is doing. If you start at a low dose and raise the dose slowly, with good monitoring and charting, you can readily see who responds too fast or too slow and at what dose.

Some doctors dont think the science is there yet and arent going to rush into using pharmacogenetic testing based on this study.

I used pharmacogenetic testing about ten years ago and the science is accurate. It tells you the persons genetic makeup, said Dr. Ernest Rasyida, a psychiatrist at Providence St. Josephs Hospital.

From a scientific point of view, he told Healthline, this was a great study. It showed that the doctor used the data 60 percent of the time.

That means that the doctor looked at the data and the medications in the green zone and chose not to use them for side effects or other reasons. Instead, they chose a drug in the red zone because of their clinical experience.

I would argue that if 40 percent of the time you are going to use your judgment and you should use your judgment then why get the test? he concluded.

In addition to depression, pharmacogenetic testing can also be used in the treatment of other non-mental health conditions, such as cancer and heart disease.

Experts say there is no risk to the patient when getting the test and the researchers said they believe it will likely benefit some patients substantially.

Pharmacogenetic results are well-known and have been for years, but the clinical practice of medicine is very conservative, so it takes a long time for clearly beneficial changes to become common practice, Merrill told Healthline. If 15 to 20 percent of patients started on a new drug can avoid a major gene-drug interaction by knowing their results, doing the test seems like a no-brainer to me.

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Depression Treatment: How Genetic Testing Can Help Find the Right Medication - Dunya News

Breast cancer treatment options have significantly expanded in the past decade, welcoming new classes of agents as well as treatments directed at specific patient populations (TIMELINE).

Many believe that these advancements in breast cancer care over the past 10 years owe much to the increased understanding of molecular factors contributing to breast cancer pathogenesis and heterogeneity.1-3

In looking back at the past decade of targeted therapy in breast cancer, Targeted Therapies in Oncology (TTO) spoke with 2 medical oncologists with extensive expertise in breast cancer about how biomarker advancements have transformed the practice of breast cancer management.

I think its fair to say that breast cancer in particular has led the way in molecular therapeutics in oncology, Dennis J. Slamon, MD, director of clinical/translational research at the UCLA Jonsson Comprehensive Cancer Center, told TTO. In part, thats because of all the investment that was made in research [and] because of defi ning this disease not just at a tissue level, but at a molecular level.

Classification of breast cancers into not just hormone receptor and HER2 positivity or negativity, but also into the luminal/basal subtypes has helped to identify treatments that may be more helpful for large groups of patients.1,3 For example, patients with basal-like disease, which is about 15% to 20% of all breast cancers, have triple-negative breast cancer (TNBC) and a poor prognosis. These patients tend to be responsive to chemotherapy treatment.1

The fact that molecular targets did not consistently translate to all breast cancers has become a key underpinning of our understanding of cancer.1 Not all patients benefi t from molecularly targeted treatments. For instance, HER2-positive breast cancer only accounts for about 25% of all breast cancer cases, thus HER2-targeted therapies may only benefi t 25% of all patients with breast cancer.

The same story is coming up again and again, not necessarily the same genes or the same targets or the same pathways, but the fact that there is a diversity of these diseases thats far beyond what we used to use to classify cancers by the tissue in which they arose, Slamon said.

Our understanding of cancer as a potentially more complex disease than previously supposed, began to develop well before 2012, explained Slamon.

That started in breast cancerbefore molecular medicine, as far back as 1899 or 98, when a surgeon recognized the fact that this disease occurred in women and the fact that it may have some hormonal component, said Slamon.4 After we found HER2, the methods of dissecting a tumor molecularly became much more sophisticated and widespread in their use and now, today, there are 14 molecular subtypes of breast cancer. And that is the underpinning of how breast cancer has led the way [in determining that patients with breast cancer] should not be treated with a one-size-fits-all approach. They should be treated with therapeutics that are directed to the appropriate subtype or the class in which they sit.

These molecular subtype characterizations have also shaped the therapeutic strategies within different breast cancer settings. Just thinking about advances in targeted therapies and how we use them to treat breast cancer in the last decade, I separate it into 2 categories1 is how we treat localized breast cancer,when our goal is to cure the cancer, so stages I to III. Most patients are being diagnosed with those earlier stages of breast cancer, Marina Sharifi , MD, PhD, assistant professor and medical oncologist at the University of Wisconsin Carbone Cancer Center, told TTO.

I think one of the major themes over the last 10 years for these nonmetastatic breast cancers is what I refer to as right-sizing therapy. We know that some of the women who have these early breast cancers can have recurrence down the road and we want to try and prevent that. So, 10 to 15 years ago, all of those women got chemotherapy, but even back then we knew that not every woman needs chemotherapy, and we knew that there were some breast cancers that could potentially benefit from more targeted types of therapies. But in the past 10 years, there have been a few developments that have allowed us to determine which women need chemotherapy and which women we can safely avoid exposing to the [adverse] effects of chemotherapy, said Sharifi.

This new prognostic ability has been fueled by advances in genomic testing.5,6 In addition to hormone receptors and molecular subtypes, other prognostic biomarkers that have been incorporated into practice include transcriptomic and proteomic levels and Ki-67 levels. Other biomarkers utilize combinations of genes to determine potential responses to treatment as well as the possibility of recurrence.

And more recently, research has turned to the use of circulating DNA and circulating tumor cells to help identify further prognostic and predictive bbiomarkers for patients with breast cancer.6

Specifically, for estrogen-driven (estrogen receptor [ER] positive) breast cancers, which are the most common type of breast cancer, we have genomic tests that are now used routinely to help us identify women who can safely avoid chemotherapy with that type of breast cancer. Both the MammaPrint and the OncoType DX are genomic tests that we know are effective in identifying which women do need chemotherapy to help maximize their chances of cure and which women have lower-risk breast cancers where the chemotherapy actually wont help them because they dont need it.7,8 That has been a huge development in the fi eld in the last 10 yearsto go from knowing that these tests were out there but not having that confirmation that we know that they predict chemotherapy benefit to having 2 major trials come out in the last 10 years that demonstrate that they can predict chemotherapy benefit, both in women who have those ER-positive breast cancers without lymph node involvement and also women who have ER-positive breast cancer with lymph node involvement. That has been a major advance for the most common type of breast cancer thats diagnosed across the country.9,10

Both the TAILORx (NCT00310180) and RxPONDER (NCT01272037) trials validated the usefulness of the 21-gene Oncotype DX recurrence score assay in patients with hormone receptorpositive, HER2-negative breast cancer. The TAILORx trial showed that among patients with node-negative disease, those with an intermediate Oncotype DX score, or intermediate risk of recurrence, could benefit from treatment with endocrine therapy alone and avoid receiving chemotherapy. Younger patients (.50 years) with a recurrence score of 16 to 25 still showed some benefit from the combination of chemotherapy and endocrine therapy.9 I n R xPONDER, adjuvant chemotherapy use was not considered necessary in most postmenopausal women with node-positive disease and recurrence scores between 0 and 25. Alternatively, premenopausal women were more likely to benefit from adjuvant chemotherapy.10

On the fl ip side, said Sharifi , somehave high-risk TNBC or high-risk HER2-positive breast cancer, those are types of breast cancer where historically we have struggled to cure women. There weve had a number of different advances. In TNBC, weve had the introduction of immunotherapies into our treatment. The KEYNOTE-522 trial [NCT03036488] showed that if wecombine pembrolizumab [Keytruda] with chemotherapy, that has significantly increased the number of women were able to cure of that higher-risk TNBC.11

Approval of neoadjuvant pembrolizumab in combination with chemotherapy for patients with high-risk, early-stage TNBC followed by single-agent adjuvant pembrolizumab by the FDA in 2021 was a signifi cant advancement for the treatment of patients with TNBC.12 Data from the KEYNOTE-522 trial were considered practice changing early on, showing a pathological complete response in 64.8% of patients treated with the regimen.11

Likewise, for HER2-positive breast cancer, we have seen the development of multiple drugs that target HER2, from trastuzumab [Herceptin] and pertuzumab [Perjeta], to ado-trastuzumab emtansine [T-DM1; Kadcyla], that have increased the number of women who were able to cure of their HER2-positive breast cancers, Sharifi said.

Slamon also commented on the proliferation of HER2-targeting therapies in addition to the expansion of other types of targeted agents, benefi tting patients in the TNBC space. [Since] our initial fi nding of HER2 and trastuzumab, now theres a ton of HER2 targeting trastuzumab deruxtecan [Enhertu] and emtansine [Kadcyla], margetuximab [Margenza]the list goes on and on of anti- HER2 therapeutics. Then there are new therapeutics for TNBC; they look at the TROP-2 target on tumor cells, and sacituzumab govitecan [Trodelvy] is the new therapeutic for that.13 As we identify new targets that we can approach with an antibody thatll attach to it, [it could be possible to] make an antibody- drug conjugate [ADC] to allow that antibody to go right to the target protein on the tumor cell and have it released internally and that takes away the systemic effect of the chemotherapy and delivers it right into the cell. Thats a whole new strategy thats coming into its own in a big way now, Slamon told TTO.

The phase 3 ASCENT study (NCT02574455) showed that sacituzumab produced a PFS and overall survival (OS) benefi t over physicians choice of chemotherapy in patients with relapsed or refractory metastatic TNBC. The median PFS with sacituzumab was 5.6 months compared with 1.7 months with chemotherapy. Median OS was 12.1 months with the ADC and 6.7 months with chemotherapy.13

The emergence of these newer targeted therapies has permitted a risk-based tailoring of neoadjuvant and adjuvant therapies in the non-metastatic breast cancer space, observed Sharifi . Another major development over the last 10 years, particularly for the [patients with] TNBC and HER2-positive breast cancers, is a shift towards neoadjuvant chemotherapy, which allows us to identify women with higher risk of recurrence after our standard pre-operative chemotherapy, and then add additional therapy after surgery to reduce their risk. For instance, that is how ado-trastuzumab emtansine is used in HER2-positive breast cancer, and there are other targeted options in this space, including olaparib [Lynparza] for women with germline BRCA mutations, she said.

We have also made great strides in precision oncology in the metastatic breast cancer space, with an expansion of different types of targeted approaches, including mutation-targeted inhibitors, immunotherapy, and ADCs. While all of these developments have helped patients live longer and better with metastatic breast cancer, I think ADCs are the most game-changing new development for treating metastatic breast cancer, Sharifi told TTO. As an example, the ADC trastuzumab deruxtecan, is a HER2-targeting agent [encompassing] trastuzumab linked to a chemotherapy that was initially found to be extremely effective for HER2-positive metastatic breast cancer, even in women who have had multiple prior treatments with different other agents. Even more importantly, however, it has recently been shown to be effective also in women who have low HER2 expression, who would previously have been classifi ed as HER2 negative.14 This has dramatically expanded the group of women with metastatic breast cancer who can benefit from trastuzumab deruxtecan to include what we are now calling HER2-low breast cancers, which are far more common than HER2-positive breast cancers. So thats been an important advance for us in the ADC space just in the last year, said Sharifi.

Data from the phase 3 DESTINY-Breast04 trial (NCT03734029) showed that patients with low HER2 expression can still possibly benefit from HER2-targeted therapy. The trial demonstrated a median progression-free survival (PFS) of 10.1 months with trastuzumab deruxtecan therapy vs 5.4 months with physicians choice of therapy in patients with HER2-low (IHC 1+/IHC 2+, ISH-) metastatic breast cancer who had received 1 to 2 prior lines of chemotherapy. The median OS was 23.9 months with trastuzumab deruxtecan and 17.5 months with physicians choice of chemotherapy.14 These findings led to the FDA approval of trastuzumab deruxtecan in this disease setting just this year.15

The Importance of Individualization

Turning to mutation-targeted therapies, this has also been an active area in metastatic breast cancer treatment in the past 5 years, including the first FDA approval of a drug targeting PIK3CA mutations, [which] are common in many types of cancer and found in almost half of women who have ER-positive metastatic breast cancer, where the drug alpelisib [Piqray] has been approved for women with this type of mutation, Sharifi told TTO.

Approval for alpelisib in breast cancer was supported by fi ndings from the phase 3 SOLAR-1 trial (NCT02437318), which showed that the PI3K inhibitor in combination with fulvestrant led to a median PFS of 11.0 months vs 5.7 months with fulvestrant in patients with PIK3CA-mutant, HR-positive, HER2-negative advanced breast cancer.16

patient with metastatic breast cancer should be getting molecular profi ling to identify possible targeted therapy options, and many patients will now have ADC treatment options that they may be eligible for at some point in their disease trajectory. For patients with localized breast cancer, I think weve also come a long way in being able to individualize therapy and avoid exposing patients to unnecessary [adverse] effects while also being able to augment treatment for patients who are at higher risk of recurrence and cure more women with this diagnosis, Sharifi said.

The basis of this personalized therapy derived from breast cancer-based research, observed Slamon. The gamechanger clearly was [the molecular advancements]. [When] looking at what is big in oncology, its this appreciation that originated in breast cancer and now has spread throughout the field of human oncology about this molecular diversity defining, a) different subtypes, and b) new potential therapeutic targets or pathways, he said.

Sharifi looks to the continued development of ADCs as a cancer treatment modality. Theres a real untapped well of potential targets that were just starting to explore in terms of developing new ADCs and combining them with targeted and immunotherapy approaches, and I think this will move the bar in how were able to combat treatment resistance, said Sharifi.

Slamons view of the future also comprises targeted strategies : As we identify more targets...therell probably be more and newer, perhaps even better, therapeutics than we have currently. Breast cancer has led this field.

REFERENCES:

1. Bettaieb A, Paul C, Plenchette S, Shan J, Chouchane L, Ghiringhelli F. Precision medicine in breast cancer: reality or utopia? J Transl Med. 2017;15(1):139. doi:10.1186/s12967-017-1239-z

2. Cocco S, Piezzo M, Calabrese A, et al. Biomarkers in triple-negative breast cancer: state-of-the-art and future perspectives. Int J Mol Sci. 2020;21(13):4579. doi:10.3390/ijms21134579

3. Low SK, Zembutsu H, Nakamura Y. Breast cancer: The translation of big genomic data to cancer precision medicine. Cancer Sci. 2018;109(3):497-506. doi:10.1111/cas.13463

4. Beatson GT. On the treatment of inoperable cases of carcinoma of the mamma: suggestions for a new method of treatment, with illustrative cases. Trans Med Chir Soc Edinb. 1896;15:153-179.

5. Hou Y, Peng Y, Li Z. Update on prognostic and predictive biomarkers of breast cancer. Semin Diagn Pathol. 2022;39(5):322-332. doi:10.1053/j.semdp.2022.06.015

6. Nicolini A, Ferrari P, Duff y MJ. Prognostic and predictive biomarkers in breast cancer: past, present and future. Semin Cancer Biol. 2018;52(Pt 1):56-73. doi:10.1016/j.semcancer.2017.08.010

7. Cardoso F, vant Veer LJ, Bogaerts J, et al; MINDACT Investigators. 70- gene signature as an aid to treatment decisions in early-stage breast cancer. N Engl J Med. 2016;375(8):717-729. doi:10.1056/NEJMoa1602253

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A Decade of Breast Cancer at the Molecular Level: Pioneering Personalized Medicine - Targeted Oncology

Home News Unspinning the secrets of spider webs

By Esme MathisOctober 19, 2022

Stronger than steel and more elastic than rubber, spider silk has the potential to transform medicine, engineering, and materials science if only we learn how to produce it.

A new global study, involving University of New South Wales scientists, has analysed the silk properties of spiders across Oceania, Asia, Europe and the USA to better understand how this natural wonder can be emulated in future biomaterials. The research, published in Science Advances, catalogued the silk gene sequences of 1098 species from 76 families.

Up until now, there was a pretty good literature set of how spider silk performs, says Dr Sean Blamires, an evolutionary ecological biologist from UNSW Sydneys School of Biological, Environmental and Earth Sciences. But what has been lacking is a way to generalise across spiders and find out what causes specific properties. Is there a link between genes, protein structures and fibres?

According to Sean, the large data set collected over five years allow scientists to create complex models, using machine learning to understand how and why specific silk properties vary between species, and even between individual spiders.

Just like the Human Genome project has given researchers the ability to identify specific gene sequence mutations that cause specific diseases, this database gives biologists and material scientists the ability to derive direct genetic causes for the properties of spider silk, he says.

There are seven types of spider silk, secreted from different glands within a spider. Out of these, dragline silk is the crowning glory. Known for its strength, durability and flexibility, dragline silk has captured scientists imagination for decades with its tantalising potential.

In a spiderweb, the dragline silk makes up the framework and the radials. Its also the silk that the spider uses when it drops off a web, says Sean. Non-web building spiders might use it to make retreats or use it for signalling with each other, while trapdoor spiders use something very similar.

In Australia, the dragline silk produced by orb-weaving spiders is so tough that it outperforms Kevlar and steels. Its tough, but also flexible.

Most materials are either one or the other, says Sean.

The study measured the mechanical, thermal, structural and hydration properties of dragline silks.

Its hoped this research will provide a blueprint for renewable, biodegradable and sustainable biopolymers. Suggested uses for this lightweight material ranges from bulletproof vests, flexible building materials, biodegradable bottles, and even a non-toxic biomaterial in regenerative medicine, that can be used as a scaffold to grow and repair damaged nerves or tissues.

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Unspinning the secrets of spider webs - Australian Geographic - Australian Geographic

Researchers have been experimenting with different ways to deliver genes to the brain to treat central nervous system diseases and tumors. One of the obstacles, however, is the ability to penetrate the blood-brain barrier while having minimal effect on the other organs in the body.

Hong Chen, associate professor of biomedical engineering at the McKelvey School of Engineering and of radiation oncology at the School of Medicine, both at Washington University in St. Louis, and her team found an effective method to overcome that obstacle using focused ultrasound intranasal delivery (FUSIN). In new research, they found that the intranasally delivered gene therapy had comparable or better outcomes than existing methods while having minimal effect on the bodys other organs.

Results of the research, led by Chen and Dezhuang Ye, a postdoctoral research associate, and collaborators, were published online in the journal eBioMedicineSept. 21. It is the first study to evaluate the potential of FUSIN to deliver adeno-associated viral vectors, small viruses used to deliver gene therapy, in a mouse model.

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A sound approach for effective gene therapy delivery to brain - The Source - Washington University in St. Louis - Washington University in St. Louis