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Powerful drugs known as BRAF-inhibitors have been crucial for melanoma patients, saving lives through their ability to turn off the BRAF protein¡¯s power to spur cancer cell growth.

However, they often work for only a year or less. Scientists know some of the DNA mutations that cause the drug resistance, but they haven¡¯t been able to determine the underlying cause of the resistance in as many as a third of these patients. As a result, identifying genomic-based follow-up therapies has been a challenge.

Researchers at MD Anderson Cancer Center have found that looking at unique ¡°protein patterns¡± in melanoma patients may help predict who will benefit from genomic-based follow-up therapies.

¡°There are patients whose DNA doesn¡¯t reveal how their melanomas became resistant to BRAF inhibitors,¡± said , instructor in Genomic Medicine. ¡°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.¡±

Kwong is first author of a paper on the BRAF study, which appeared recently in the online edition of the .

¡°BRAF-inhibitors are effective in melanoma patients whose tumors have a ¡®hot spot¡¯ mutation in the BRAF cancer gene,¡± said Lynda Chin, M.D., chair of Genomic Medicine, and corresponding author on the JCI paper. ¡°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.¡±

Kwong and Chin¡¯s team analyzed BRAF inhibitor resistance using a BRAF mouse melanoma model and human tumor biopsy samples. They found that such ¡°proteome profiling¡± can provide a rapid view of BRAF-inhibitor resistance patterns in melanoma patients at a fraction of the cost of DNA or RNA sequencing.

In addition to these findings, the study also suggested the potential of using RNA and protein data as candidate ¡°biomarkers¡± to help predict how long a patient will respond to BRAF inhibitor treatment so that combination or second-line therapies can be considered in a more personalized manner.

¡°These biomarkers include genes that track how fast the tumors are growing and how active the immune system is in the tumor,¡± said Kwong. ¡°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.¡±

The scientists caution that the study size was relatively small and will require additional analysis of much larger cohorts of patients.