Researchers from The University of Texas MD Anderson Cancer Center may have found a way to accurately predict which patients will be more likely to respond to genomic-based follow-up therapies by interpreting unique “protein patterns” in melanoma patients.
BRAF-inhibitors are strong and powerful drugs used to treat melanoma patients due to their capacity to turn off BRAF protein’s power to stimulate cancer cell growth. However, these drugs only work for approximately one year since patients carry DNA mutations that lead to drug resistance (approximately one third of melanoma patients). The scientific community is seeking to overcome this obstacle and discover genomic-based therapies to successfully treat the disease.
“There are patients whose DNA does not reveal how their melanomas became resistant to BRAF inhibitors. So we looked at patterns of changes in 150 proteins which can give clues to the causes of resistance, even when DNA sequencing data is uninformative,” said Dr. Lawrence Kwong, who authored the results published in the Journal of Clinical Investigation (JCI).
Lynda Chin, M.D., correspondent author of the study, explained: “BRAF-inhibitors are effective in melanoma patients whose tumors have a ‘hot spot’ mutation in the BRAF cancer gene. Unfortunately, almost uniformly, these patients develop resistance to the drug. Therefore, figuring out how melanoma gets around the drug is a critical first step in identifying an alternative therapy for these patients once resistance develops, or better yet, a way to treat these patients with combinations that prevent the emergence of resistance.”
Using mice models of BRAF melanoma in addition to human tumor biopsy samples, investigators assessed BRAF inhibitor resistance, concluding that specific proteome profiling can provide insights into BRAF-inhibitor resistance. Through DNA or RNA sequencing it is possible to predict how long a patient will respond to these treatments and how second-line approaches can be optimized depending on each individual patient’s biomarkers.
“These biomarkers include genes that track how fast the tumors are growing and how active the immune system is in the tumor. This raises the possibility that pre-treatment biopsies can be used to guide decisions on targeted agents or immunotherapies that may be most effective for that individual patient,” noted Dr. Kwong.