Cancer

Pancreatic cancer has the highest mortality rate of all major cancers. It is especially difficult to treat because the tumors grow so quickly and are constantly evolving. But patient-derived organoids could change all that. In this emerging biotechnology, researchers obtain a small sample from a patient biopsy and use it to grow 3D tissues in the lab. These “organoids” act as miniature models of the patient’s pancreatic tumor and can be used to quickly evaluate which cancer drugs might work best for them. A recent study by Assistant Professor Dannielle Engle, postdoctoral researcher Jan Lumibao, and colleagues provided critical insights into the robustness of patient-derived organoids as a clinical model of pancreatic cancer. They found the organoids’ gene expression and drug responses were not affected by the brand of extracellular matrix used in the cell culture. Data like this increases confidence that clinical conclusions are reliable across different labs and batches of organoids. They also identified one matrix brand that sped up the growth of tumor organoids, making it particularly well-suited for the fast pace of pancreatic cancer treatment protocols.

Immunotherapy has revolutionized the way we treat cancer in recent years. Instead of targeting the tumor itself, immunotherapies work by directing patients’ immune systems to attack their tumors more effectively. Still, fewer than half of all cancer patients respond to current immunotherapies, creating an urgent need to identify biomarkers that can predict which patients are most likely to benefit. Associate Professor Diana Hargreaves, postdoctoral researcher Matthew Maxwell, and colleagues have done just that, revealing that mutations in a gene called ARID1A make patients more likely to respond positively to immune checkpoint blockade—a type of immunotherapy that works by keeping cancer-fighting immune cells turned “on.” The ARID1A mutation prompts an antiviral response that pulls more cancer-fighting immune cells into the tumor, and because the gene is present in many cancers—endometrial, ovarian, colon, gastric, liver, and pancreatic—the biomarker could have a huge impact on identifying patients for specific immunotherapies. The findings also encourage the development of drugs that target ARID1A and related proteins as a way of sensitizing other tumors to immunotherapy.