Advanced Rare Cancer
In his talk on targeted therapy for rare cancer, Glen Weiss, M.D., associate investigator in the cancer and cell biology division at Tgen clinical research services, described work carried out at the University of Arizona College of Medicine on what makes a successful strategy for developing molecular targets and companion therapies in cancer.
The main problem in cancer is that not all patients (or the cancers they have) are the same. Yet currently, patients with the same cancer are primarily treated with the same type of chemotherapy. This therapy, not surprisingly, produces inconsistent results. Identifying markers that can be used to better target cancer with therapies most likely to work can improve results.
Some initial work that has come from Dr. Weiss’s group is in patients with advanced cancer. The team evaluated what potential targets a tumor might have for treatment—not necessarily those approved for a particular cancer. In conjunction with the Molecular Profiling Institute, which was a spinout from Tgen, they surveyed more than 110 patients, looking at gene expression in their tumors, as well as protein staining, picking out some common genes that predict response to certain drugs. Almost 100% of patients had a target for which there is a drug on the market.
Following up on that work, Dr. Weiss and his team conducted a prospective study on patients with advanced cancer. They analyzed tumor biopsy samples for genes and proteins in the cancer to try to identify a possible treatment, even if that treatment did not match their original cancer diagnosis. For example, if someone had breast cancer, and their tests indicated they could benefit from a colon cancer regimen, then they were given that treatment.
The results of this study were that 27% of the patients had an improvement of at least 30% greater duration of control of their cancer, compared to their last type of conventional cancer treatment.This confirms that genetic profiling can be useful for cancer treatment. The utility is especially attractive for rare cancers where there is less information to indicate which treatment is best.
Dr. Weiss also presented research into the use of locking signaling of Hedgehog pathway to improve outcomes for basal cell carcinoma (BCC), again showing some modest success in personalizing therapy for patients with advanced BCC. “So to have these real dramatic blockbuster successes with drugs, instead of just treating everyone with the more common cancers all the same, we’ll have to delve into the biology of what makes those individual cancers unique in each patient.
“We’re going to have to conduct much larger searches, paying attention to identified tumor targets, to find the small group of patients that will get great results with a treatment; rather than treat large groups of patients without evaluating their tumor targets, which results in minimal to no positive results.”