Melanoma: Assaying Multiple Proteins Helps Identify BRAF-Inhibitor Resistance

Linda Chin, MD Department Chair, Department of Genomic Medicine, Division of Cancer Medicine The University of Texas MD Anderson Cancer Center Houston, TXMedicalResearch.com Interview with:
Linda Chin, MD

Department Chair, Department of Genomic Medicine, Division of Cancer Medicine
The University of Texas MD Anderson Cancer Center
Houston, TX

Medical Research: What is the background for this study? What are the main findings?

Dr. Chin: BRAF inhibitors have worked very well against melanoma in the clinic, but when the tumors relapse on treatment, it is not always clear what causes it. Without this information, it can be difficult for doctors to identify specific second-line therapies likely to overcome the drug resistance. In this study, we used both mouse and patient melanoma samples to identify patterns of selected protein levels that can categorize modes of drug resistance when other assays such as DNA sequencing are uninformative. We hope that this information can provide missing clues for clinicians.

Medical Research: What should clinicians and patients take away from your report?

Dr. Chin: Our report emphasizes the need for multiple assays to cover all angles when it comes to understanding drug resistance. From other reports plus ours, anywhere from a quarter to over a third of BRAF inhibitor-resistant melanomas have unknown causes of resistance when looking only at RNA and/or DNA. Our study shows that looking at over a hundred carefully selected proteins in the tumor can help fill in that gap. This assay is also relatively quick and cost-efficient.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Chin: In the future, we recommend that looking at many proteins together, rather than a few at a time, provides a powerful way to triangulate information. This is further helped by looking specifically at activated or inactivated versions of key proteins. We showed that the overall assay was more accurate than when only looking at two or three, or only at RNA, which is what is commonly done.

Citation:

Co-clinical assessment identifies patterns of BRAF inhibitor resistance in melanoma.

Kwong LN, Boland GM, Frederick DT, Helms TL, Akid AT, Miller JP, Jiang S, Cooper ZA, Song X, Seth S, Kamara J, Protopopov A, Mills GB, Flaherty KT, Wargo JA, Chin L.

J Clin Invest. 2015 Feb 23. pii: 78954. doi: 10.1172/JCI78954. [Epub ahead of print]

 

MedicalResearch.com Interview with:Linda Chin, MD (2015). Melanoma: Assaying Multiple Proteins Helps Identify BRAF-Inhibitor Resistance