When searching for oncology precision medicine treatment options, every minute matters. Technological advancements, including the use of 3D cell culture, have opened the doors to faster, more reliable drug development. By mimicking the biological similarity and complex heterogeneity of the actual tissue, 3D organoid models enable researchers to better predict outcomes of treatment options, which is especially helpful in testing drugs on cancers that have metastasized to other organs. Now more than ever, scientists are leveraging the benefits of organoids–from predicting treatment responses on cancerous lung and colon cells, to improving the chances of successful organ transplant—instilling hope for patients worldwide.
Predicting Treatment Responses
When time is of the essence, it helps to have access to the right tools to overcome workflow challenges. Those studying small cell lung cancer (SCLC) know collecting tissue for treatment screening is challenging, even more so when fighting brain metastases. SCLC is a heterogenous, aggressive cancer with poor survival outcomes; most patients only live about a year after diagnosis. Rapid tumor growth and low survival rates make obtaining viable tissues extremely difficult. In fact, tissue scarcity for primary and metastatic SCLC has been a long-standing obstacle to the molecular characterization of the disease–an issue that Amanda Linkous, PhD, Scientific Manager at the NCI Center for Systems Biology of Small Cell Lung Cancer at Vanderbilt University, knows all too well.
“Organoids are helpful because we can generate miniature tumor specimens in a dish within a microenvironments that mimic human organs,” says Dr. Linkous. “These are tumors that otherwise would not be available to us – aside from a clinic specimen every few months. Now, we can make them on a monthly basis on a very large scale, which allows us to gather more information which would otherwise be very limited if we had to rely solely on specimens from the clinic.”
Organoids are increasingly used in labs around the world, as they enable the researcher to visualize and manipulate organoid cells in real time. Even more, organoids modeling the lung and the brain can be grown in as little as 4-6 weeks alleviating the need for more invasive tissue procurement procedures.
Reflecting tissue heterogeneity is also important for treatment testing and understanding the longer-term success rate of cancer treatments. “Despite the fact that colorectal cancer is a somewhat textbook disease, the therapy has remained the same for over 40 or 50 years,” says Francesco Cambuli, PhD, Senior Scientist at the New York Genome Center. Like lung cancer, in stage IV colorectal cancer, studying the primary tumor is insufficient; the metastasized tumors must be addressed as well. Organoids are well-suited to study treatment responses across organ systems and are being leveraged to predict tumor behavior and resurgence even in different subtypes of the same cancer. According to Dr. Cambuli, "In one particular type of tumor, there may be five different heterogenic types. The benefit of organoid modeling is that it can be used to study and treat all different types of colorectal cancer."
Improving Organ Transplant Success
Like cancer, organ transplantation is a difficult feat that is bound by time, especially in vital systems like the liver, as there are no established methods to restore cell function. In fact, most tissue transferred during transplant is lost due to graft failure in the first days after transplant. Precision medicine and 3D cell culture methods present a unique opportunity to supply the body with complex, differentiated liver cells, grown from a human donor and treated to fight disease, that can be transplanted into patients who have lost liver function. Spheroid cultures have demonstrated improved hepatocyte function and resiliency during transplantation through the portal vein or umbilical cord compared to cells grown in 2D cultures.
Nino Faleo, PhD, Senior Scientist at Ambys Medicines, is leveraging 3D spheroid technology to push the boundaries of what’s possible. “By increasing the complexity of the 3D spheroids we can better mimic the physiology of the liver and enhance hepatocyte function,” says Dr. Faleo. “It’s exciting to think about the big picture. Having more accurate disease models enables faster drug screening, which decreases the time and ultimately the costs needed to develop new treatments for patients.”
Collaboration Drives Innovation
Innovation is made possible by lessons learned through trial and error, and in this case, by passionate scientists and experts who work together to find solutions. Companies like Corning Life Sciences work hand-in-hand with customers to overcome barriers to discovery. “I’ve had a great experience working with Corning specialists,” says Dr. Faleo. “At the beginning, they offered their expertise and brought a lot of product knowledge to the table–which shortened my initial trial period.”
And when it comes to perfecting workflows, Dr. Linkous says she can rely on the technical advice from Corning to produce more consistent results over time. “At one point, we had an issue that was causing some of the organoids to stop expanding during a particular step,” she says. “It’s nice to collaborate with experts who know how to optimize lab staples, like Corning® Matrigel® matrix, to overcome those physical challenges.”
Precision medicine has come a long way since the Human Genome Project–the accuracy in predicting an individual’s response to treatment has significantly increased by using patient-derived organoids versus the patient-derived cell lines of the past. Scientists have made headway testing the efficacy of anti-cancer drugs on patient avatars, but the possibilities go far beyond drug discovery alone. Advancements in precision medicine and predictive science provide a small glimpse into patient-centric care of the future, which will undoubtedly change the healthcare industry as we know it.