Friday, July 12, 2024

New Way to Treat Drug-Resistant Melanoma

Researcher at Sanford-Burham have found a new way to treat drug-resistant melanoma, and this new study was published in Cell Reports. The study gives new insight into how there are molecular changes that occur that end up leading to a resistance that is commonly found in prescribed drugs called BRAF inhibitors. The findings from this study suggest that there might be a new approach to treating patients who have BRAF inhibitor-resistant melanoma. The senior author of this study is Ze’ev Ronai, Ph.D., scientific director of Sanford-Burnham’s La Jolla campus.

melanoma health

Melanoma is the deadliest type of skin cancer, which ends up killing more than 8,000 people in the United States every year. 50 percent of the melanoma tumors are driven by the changes in the BRAF gene, and most patients are given BRAF inhibitors to treat the condition. The success of this treatment is limited because most of the melanoma tumors become resistant to the drugs after a few months, and that means the outcome for these patients is often not very good.

The melanoma tumors develop the resistance to the BRAF inhibitors by using the alternate pathways that promote cell growth. The study ended up finding a different pathway, which is JAK1, and this is the driver for the resistance to the BRAF inhibitors. The study is suggesting that if there is a treatment that targets the JAK1, it could mean that the resistance could be overcome. If that was to happen, then the response to the BRAF inhibitors would turn out better in the long run, and that would improve the overall prognosis for people with this type of melanoma. JAK1 has been studied for a long time, and it is involved in the control of the cell growth, differentiation, apoptosis, inflammation, and immune response. However, it was not known that JAK1 was responsible or played a role in melanoma or the resistance to therapy.

The researchers analyzed the BRAF inhibitor resistance in the melanoma cell lines, using both mice that had human melanoma tumors, and in the human tumor biopsy samples. The researchers ended up finding higher levels of JAK1 in the resistant tumors, which then caused the epidermal growth factor receptor to express itself more. This receptor is known to promote cell proliferation. The JAK1 increases were due to lower levels of the protein that regulates the expression, which was ubiquitin ligase RNF125.

Keith T. Flaherty, M.D., associate professor, Harvard Medical School, and director of Developmental Therapeutics, Cancer Center said, “ By helping us understand that lower levels of RNF125 confer resistance to BRAF inhibitors, we have a new strategy to stratify patients for currently approved therapy versus participation for human clinical trials to investigate whether targeting JAK1 will be more effective in patients whose tumors exhibit reduced RNF125.”

It is likely that more studies will be done in order to determine the best course of treatment of these types of tumors, which can help ensure these new targeted treatments will be safe and effective for people with the resistant melanoma.

Jeanne Rose
Jeanne Rose
Jeanne Rose lives in Cincinnati, Ohio, and has been a freelance writer since 2010. She took Allied Health in vocational school where she earned her CNA/PCA, and worked in a hospital for 3 years. Jeanne enjoys writing about science, health, politics, business, and other topics as well.


Please enter your comment!
Please enter your name here