UCLA scientists have recently released study findings which may hold important implications in the field of metastatic melanoma research. The study entitled, “Non-genomic and Immune Evolution of Melanoma Acquiring MAPKi Resistance“, was published in the journal Cell, and may possibly lead to new tests for the early detection of drug-resistant tumor cells, as well as, treatments that suppress possible resistance to targeted therapies.
The study was conducted in the laboratory of, Dr. Roger Lo, MD, PhD, Associate Professor, Departments of Dermatology and Molecular and Medical Pharmacology, Jonsson Comprehensive Cancer Center, UCLA. Dr. Lo’s research is focused on understanding the genes involved in the pathogenesis of melanoma, and understanding the mechanisms involved that lead to drug resistance in certain tumor subtypes.
Dr. Lo and his team aimed to uncover the mechanisms responsible for both treatment resistance and abnormal immune responses that lead to treatment resistant melanoma in patients undergoing therapy. The team studied melanoma by three different methods:
- Analyzing samples of patients’ melanoma tumors both before they underwent therapy and when the disease recurred.
- Modelling drug resistance by growing melanoma cell lines from patients’ tumors.
- Analyzing tumor genes utilizing genomics (multiple gene mutations can be studies simultaneously) and epigenomics (detects changes within gene functions throughout the tumor).
The findings showed that treatment resistance can evolve at the same time as a weakening of the body’s immune defenses and that this has a significant impact on the patient’s ability to successfully respond to prescribed drug regimens.
In a University press release about the study, Dr. Lo, stated “Only cancer cells, not immune cells inside the tumors, accumulate gene mutations. Mutational profiling alone cannot tell us about the state of the intratumoral immune cells and their changing states when melanoma becomes resistant to therapy.”
When asked about what he hopes will result from the discovery, Dr. Lo, said, “that the findings will prompt drug development and clinical studies based on epigenetic or gene expression and immune targets in combination with mutation-targeted therapies.”
This study was funded by the National Cancer Institute, the Melanoma Research Alliance, the SWOG/Hope Foundation, the Cancer Research Institute and Stand Up to Cancer