A $3.2 million grant from the NIH will support the creation of Melanoma Resistance Evolution Atlas (MREA). Ultimately, researchers hope to develop novel approaches to prevention and treatment of resistant melanomas.
Led by Dr. Roger Lo, professor of medicine and molecular and medical pharmacology at the David Geffen School of Medicine at UCLA, and Alan Tackett, professor of biochemistry and molecular biology at University of Arkansas for Medical Sciences (UAMS) Winthrop P. Rockefeller Cancer Institute, researchers will implant fragments of tumors from patient biopsies to grow in specialized mice. This will allow the team to test different combination therapies.
The team will then examine the unique characteristics and behaviors of each patient’s tumor, before and after it is treated with MAPK-targeted drugs as well as when it stops responding. They will use proteogenomic and single-cell analyses to identify new drug targets to design future experimental combination therapies.
“We will use current and newer MAPK-targeting agents as foundations to add other types of drugs,” says Dr. Lo. “Better MAPK inhibitor-based combination treatments will benefit not only patients with melanoma but also a large fraction of patients with other types of common and aggressive tumors such as lung and colorectal cancers.”
Virtually all cutaneous melanomas display genetic alterations that activate a cancer-driving pathway called MAPK. About half of advanced melanomas feature BRAF mutations, and some BRAF mutated melanomas respond to existing MAPK-targeted therapy. However, many develop resistance over time, leading to clinical relapses and more aggressive cancers. For the other half of patients with melanomas lacking the specific BRAF mutations, there currently are no FDA-approved options for treatment with MAPK-targeted drugs.