By Ding Wang, MD and Catherine Jenovai
Every day our bodies are exposed to various injuries that may damage our cells. The damaged cells with certain types of genetic defects are tagged as abnormal and removed by our immune system. If something goes wrong and the cells are not removed by our immune system, they may become cancer cells over time. Sometimes cancer cells figure out a way to hide from our immune system by producing a molecule called PDL-1 (programmed death ligand-1), which uses camouflage to trick the immune system into thinking they are healthy cells.
Immunotherapy for cancer treatment
Anticancer drugs called immunotherapy have been developed to combat this trick. One type of immunotherapy, called Anti-PDL-1 antibodies, binds to the PDL-1 molecule on cancer cells. This allows the patient’s immune system to find, unmask, and destroy cancer cells. The drug MEDI4736 is an Anti-PDL-1 antibody that is being tested in research in combination with other drugs to treat certain cancers.
DNA damage repair, PARP inhibitors, and cancer
PARP inhibitors are drugs that specifically target cancer cells with mutations in some of the genes involved in repairing damaged DNA. In people with BRCA mutations, the BRCA repair pathways do not function properly and are unable to repair certain types of DNA damage. This can lead to cancer developing. By treating with a PARP inhibitor, such as olaparib, both DNA repair pathways will be shut off in the cancer cells, which makes the cancer cells more likely to respond to treatment.
Mediola is an important clinical trial. It’s a Phase I/II study combining both of these mechanisms to target cancer cells. First patients received the PARP inhibitor Olaparib for 4 weeks, then they will receive both Olaparib and an immunotherapy drug called MEDI4736 (known as an “Anti-PDL-1” drug) that helps the immune system attack cancer cells. All patients enrolled in this study will be given the study medications, a combination of both MEDI4736 and olaparib, after the initial four-week period of taking olaparib alone.
Patients with a BRCA mutation who are diagnosed with platinum-sensitive relapsed ovarian cancer or HER2-negative metastatic breast cancer are eligible. Patients with relapsed small cell lung cancer or gastric cancer (including gastroesophageal junction adenocarcinoma) would be eligible to participate even if they don’t carry a BRCA mutation. Patients who participated on PARP inhibitor trials, but were randomized to receive placebo or physician’s choice therapy, are allowed to participate in MEDIOLA.
Learn more about MEDIOLA
For more information about MEDIOLA, call 877-400-4656 or visit cancerstudylocator.com/azo/trial/113408/.
Dr. Ding Wang is the Medical Director of the Clinical Trials Office at the Henry Ford Cancer Institute at Henry Ford Hospital in Detroit, MI. Dr. Wang works with all treating physicians and meets with all Phase 1 patients, ensuring that they and their families understand and play an important role in the care plan by sitting down with them to review radiology images and progress. Building relationships through a solid foundation of trust is critical to Dr. Wang, and nearly 100 percent of his patients give him the highest satisfaction rating via Press Ganey surveys. Dr. Wang is a tumor board member for CNS, GYN, Thyroid, Melanoma, and is on the Precision Medicine Task Force at Henry Ford Hospital. He is dedicated to the growth of clinical trials operations, and is committed to offering more novel therapeutic alternatives for patients who cannot receive standard of care therapies.
Catherine Jenovai is a manager in the clinical trials office at Henry Ford Hospital. She is the lead coordinator of the Phase I program working under Dr. Wang.
Tags: brca, BRCA 1, BRCA 2, brca research, BRCA2, breast cancer, breast cancer treatment, ovarian cancer, ovarian cancer treatment