President Richard Nixon declared war on cancer in 1971 with the signing of the National Cancer Act. Despite more than a half-century of scientific breakthroughs, cancer remains the second-leading cause of death in the United States.
The challenge for scientists is that cancer is not universal. There are more than 100 types of cancer, and each of these cancers can have various subtypes. Even the same cancer type is not the same in any two patients. This is what makes the war on cancer a truly personal battle.
Now researchers at the University of Arizona Health Sciences are turning to a new tool in the fight against cancer and other rare diseases: organoids.
Organoids are tissues or miniature tumors grown in the laboratory, said Yana Zavros, PhD, professor and associate head for research in the UArizona College of Medicine Tucsons Department of Cellular and Molecular Medicine and a member of the UArizona Cancer Center.
Organoids can be grown from stem cells or from patient-derived tissue. With a three-dimensional structure, organoids mimic the genetic and biological functions of organs and provide researchers with an under-the-microscope look at how tumors may behave in the body. With this information, investigators can create tailored therapies for more effective responses in patients.
To conduct this research, UArizona Health Sciences researchers collaborate with the Biology Development and Research of Organoids, or BioDRoid, service provided at the UArizona Cancer Center. Led by Dr. Zavros, BioDRoid provides the expertise required to grow organoids from stem cells and patient tissue samples. The facility collects and catalogs healthy cells, tumor cells and immune cells for many conditions. The organoids can then be directly studied, tested with drugs or be cryopreserved for future investigation.
The complexity of the organoids we grow in the lab closely mimic the patients own tumor behavior and how it responds to drugs in the body, Dr. Zavros said. Organoids allow us to look at the tumor microenvironment at a higher resolution. This helps us identify targeted therapies that can be tested with drugs to determine the safest and most effective treatment prior to clinical use in the patient.
A single tissue biopsy can produce a seemingly endless number of organoids for scientists to use for studying a particular type of cancer or disease.
Once a tissue sample is received from the clinic, BioDRoid will process the tissue and place it in an incubator to allow the organoid cells to begin growing. For aggressive tumors, organoids will develop within 24-48 hours. Within a week, hundreds of organoids will have grown. Researchers can continue expanding the organoids into the thousands until they have enough for a study. The ability to cryopreserve live organoids makes them a limitless resource.
The organoids offer several advantages to other common methods. One of those benefits is less reliance on animal model studies since the researchers can work with live human tissue. Organoid modeling is faster and easier than animal modeling, and it maintains a more realistic human physiology.
Organoids are also useful to researchers because what can be learned from them has potentially larger societal impacts than other methods, such as using cell lines.
Organoids give us a better representation of the cellular diversity of tumor, said Dr. Zavros. Cells lines come from one patient and are not representative of the entire cell population. We cant develop effective therapies based on five cell lines because those five patients may not be representative of the full population of patients that have a disease.
Organoids are tissues or miniature tumors grown in the laboratory.Yana Zavros, PhD
Instead, organoids are valuable to researchers because they can be grown to mimic all the various subtypes of a specific disease. This leads to delivering more precise treatments to more people.
Precision medicine to us is not collecting a tissue sample from every single person. That is not feasible, Dr. Zavros said. But what we can do is stratify and subtype organoids similar to how there are subtypes of cancers. This is important because we know that these subtypes of cancers are more responsive to certain therapies. We hope that the end result is that we can discover therapies that will help patients.
One of the examples of this translational research is in a pancreatic cancer clinical trial led by Rachna Shroff, MD, MS, professor and associate dean of clinical and translational research for the College of Medicine Tucson and medical director of the clinical trials office at the UArizona Cancer Center. Dr. Shroffs trial is studying a new drug combination for pancreatic cancer patients whose tumors have been resistant to standard therapies.
For the study, Dr. Shroff has collected patient tumor biopsies both prior to the new treatment and during the treatment. In collaboration with Dr. Zavros laboratory, the biopsies are being used to grow organoid cultures to better understand the resistant cell populations within the tumor. The findings could eventually lead to new standard treatments for this population of pancreatic cancer patients.
One of the limiting factors in new drug discovery trials is the balance between a drug being effective at fighting off the harmful cells while not destroying the healthy cells. This balance becomes critical in the gut where the lining of the stomach, intestine and colon absorb nutrients while eliminating harmful bacteria. However, this lining is constantly replacing old cells and regenerating itself, making it susceptible to disease if it regenerates abnormally.
Curtis Thorne, PhD, assistant professor of cellular and molecular medicine at the College of Medicine Tucson and a member of the UArizona Cancer Center, leads a research laboratory focused on understanding of how the lining of the gut maintains itself. His lab has been using organoids for the past six years to gain a clearer picture of what is taking place in the gut and how drugs can be developed to treat diseases like colon cancer.
My lab views organoids as a drug-discovery platform, Dr. Thorne said. The way to think of them is as mini guts in tiny wells. Were able to put these miniature guts into 96 or 384-well plates. That allows us to do lots of experimental conditions to figure out how they grow and to discover new therapeutics that would prevent tumor organoids from growing.
Dr. Thorne explains that barrier function problems, such as those in the lining of the gut, can be deadly and that drug toxicity is of particular concern for patients undergoing treatment. By using organoid models, Dr. Thornes research team can better predict which drugs will be safest for further investigation.
We are seeing that we can predict drug toxicity at a much earlier stage of the drug development. Generally toxic compounds can be triggered early, and we can focus our efforts on those that are expected to have better toxicity profiles when tested in patients, Dr. Thorne said. We think organoids are the best platform for demonstrating tumor behaviors in a dish in a form that we can screen drugs and identify better lead compounds that are more likely to work once they hit the clinic.
Read more from the original source:
Miniature organs driving precision medicine and new drug discovery - University of Arizona
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