The ability to test patients’ cancers for individual differences, mainly at the genetic level, and to make treatment decisions based on those differences is the hallmark of precision medicine, and Vanderbilt University Medical Center (VUMC) is among the leaders of this new approach to diagnosis and treatment.
“Nationwide we’re seeing great promise with this approach and we’re seeing it first in cancer,” said Jennifer Pietenpol, Ph.D., executive vice president for Research at VUMC and the director of Vanderbilt-Ingram Cancer Center (VICC), during a recent community forum.
Nearly 100 patients, caregivers and members of the community gathered at the Vanderbilt Student Life Center for the educational session.
Moderator Carlos L. Arteaga, M.D., director of the Center for Cancer Targeted Therapies and the Breast Cancer Program, told the audience that precision medicine in cancer starts with the identification of actionable gene alterations in tumor DNA that can be used to select therapies that are most effective.
Arteaga, also the Donna S. Hall Professor of Breast Cancer, said many drugs “hit the dust” in previous clinical trials because they weren’t tested correctly, that is by not selecting the patients who, based on their tumor genetic alterations, were likely to respond to the tested drug.
“New targeted anti-cancer drugs are now tested mainly in patients with specific tumor gene mutations that potentially predict drug efficacy against those cancers but not in tumors without those gene alterations. In my opinion, this project called cancer precision medicine is the most important enterprise in cancer research in our generation and all of us have joint custody of it.”
The panelists, nationally recognized medical researchers and oncologists at VICC, explained that standard therapies like surgery, chemotherapy and radiation are still effective and often cure early-stage cancers. But for cancers that recur or that are diagnosed at a late stage, DNA testing of the tumor to search for actionable mutations is warranted.
Breast cancer was one of the first specialties that benefited from identification of high levels of the HER2 oncogene, an alteration in a gene that encodes a protein. Twenty percent of breast cancer patients have tumors with high HER2 levels (so called HER2+ breast cancers) which used to be the most lethal subtype of this cancer. But thanks to precision medicine and trials with anti-HER2 drugs in the last 20 years, there are now four drugs that target HER2 and inhibit the protein in different ways. Now nearly 90 percent of patients with early operable HER2+ breast cancer are likely to be cured of their disease.
Kimryn Rathmell, M.D., Ph.D., director of the Division of Hematology and Oncology, who specializes in urologic cancer, said that precision medicine is coming for cancers of the kidney, bladder, prostate and testis, but has been slower due to the complexity of the diseases. Kidney cancer, for example, is really comprised of 15 different named cancer types, which can be divided even further when looking at associated gene events, which sounds daunting.
“We now have an opportunity to take them one by one because of big advances in precision medicine. We can slice and dice these in different ways and there is some order in this chaos. We can look at a profile of a tumor and predict what it is,” Rathmell explained.
VICC is also opening clinical “basket trials” to test therapies that target a gene mutation no matter where the tumor started in the body. So patients with breast cancer, colon cancer and melanoma might all be treated with the same investigational drug if the tumors all have the same targeted mutation.
New gene testing capabilities, novel clinical trial designs and targeted therapies are all being utilized to give patients better outcomes.
“Now more than ever, we have the tools to outsmart the cancer and continue to reduce cancer mortality,” Arteaga said.
Other members of the panel included Douglas Johnson, M.D., Ingrid Mayer, M.D., Justin Balko, Pharm.D., Ph.D., Mia Levy, M.D., Ph.D., and Christine Lovly, M.D., Ph.D.
