Combination molecules with BRAF inhibitors may help overcome drug resistance in melanoma patients
January 07, 2020
"Normal cells have physiologic safety mechanisms to avert death and this is taken to a higher level by the cancer cell to serve its growth agenda, making single agent targeted therapy insufficient," Lo said. "We have to block several roads, which is what is behind our approach to developing combination therapies. The key was to figure out how to combine the molecules so that the cancer cannot get around them. Why wait for the cancer to escape? Let's block all the pathways right from the start."
Lo said this study highlights the need not only to identify mechanisms of acquired resistance to targeted inhibitors, but also to understand the signaling network associated with each mechanism to generalize potential translatable approaches to overcome drug resistance.
Once the right combinations of drugs were used together, the inhibitors "consistently triggered cell death in a highly efficient and consistent manner," the study states. "Together, our findings offer a rational strategy to guide clinical testing in pre-identified subsets of patients who relapse during treatment with BRAF inhibitors."
Lo said a clinical trial could be planned that first examines the patients' cancers to identify the resistance mechanisms at play. Those patients could then be funneled into a study pairing the inhibitors that target those specific pathways. Patients with other resistance mechanisms at work would be placed in studies testing inhibitors specific to their resistance mechanisms.
The next step, Lo said, is to identify all the mechanisms of resistance in this form of melanoma.
According to the American Cancer Society, melanoma incidence rates have been increasing for at least 30 years. This year alone, more than 68,000 Americans will be diagnosed with melanoma, with 8,700 dying from their disease.
Source: University of California - Los Angeles Health Sciences