Targeted therapy and checkpoint blockade immunotherapy significantly improved the therapeutic effect of melanoma. Unfortunately, resistance to these therapies remains a limitation. New anti-tumor therapies targeting MCL1 anti-apoptotic protein have shown impressive responses in hematological cancers, but have not been evaluated in melanoma.
Scientists at the Centennial Research Institute have reported a new strategy against melanoma, which is one of the most dangerous types of skin cancer, causing approximately 1700 deaths in Australia each year.
Drugs can be used to inhibit two different proteins. The researchers found that these two proteins may effectively kill melanocytes by inducing apoptosis (a process of cell self-destruction that occurs when cells are no longer needed).
This new treatment strategy may benefit a group of melanoma patients who do not respond to targeted therapy or immunotherapy.
The study ’s lead author, Dr. Hsin-YiTseng, a researcher at the Centennial Institute ’s melanoma oncology and immunology program, said, “Because high levels of anti-apoptotic proteins or ‘protective agent’ proteins are found in melanoma cancer cells Therefore, inducing apoptosis has proved extremely difficult. “
Dr. Hsin-YiTeng said,” These protective proteins help melanoma cells survive and grow, and in some cases will help resist advanced medical treatment. “
In this study The researchers jointly inhibited the protein MCL1, as well as proteins from the bromine domain and the super-outer terminal (BET) family. Both of these substances are believed to play a key role in protecting and supporting melanoma cells in the body.
Dr. Hsin-YiTseng said, “Our research shows that the combined use of BET and MCL1 inhibitors is very effective in killing melanoma. The protective ability of BET and MCL1 proteins decreases under the action of drug inhibitors, and causes cancer cells to destroy themselves. “
Dr. Jwssamy Tiffen, a senior co-author of this study, is also a member of the Centennial Institute Melanoma Oncology and Immunology Program. She said that the team ’s research is of great significance and can provide a potential new treatment strategy for melanoma patients.
Dr. Tiffen said, “About half of melanoma patients do not respond to immunotherapy, and most patients will develop acquired resistance to targeted therapy. Our study tested a large number of human melanoma cell lines and mouse models. In these cases we have seen a substantial decrease in melanoma, which indicates that this study will enter the next stage of development. “
This study was published in the” International Journal of Cancer “.
Melanoma is the most common cancer in young Australians, and these people range in age from 15 to 39 years old.
In this study, scientists were able to prove that BET and MCL1 inhibitors can effectively reduce the migration and invasiveness of melanoma cells. This is achieved by successfully inhibiting the interaction between two proteins involved in intracellular transport (the process of molecules passing through the cell membrane of living cells).
This study is significant because metastasis is the process by which cancer metastasizes to a new part of the body and is the main cause of death for melanoma patients.
“We have known that for some time, melanin and RAB27A protein are bound together, and this process may be crucial to help melanoma cells spread in the body,” Guo, the lead author of the study and a PhD researcher at the Centennial Research Institute (Immune Imaging Project) Mr. Dajiang said, “By blocking the binding of these two proteins with a recently developed blocking compound (BMD-20), we were able to successfully restrict the movement and invasion of melanoma cells.” Our findings indicate that specific targets The new drug that interacts with rab27a is a promising target for the treatment of advanced melanoma. “
Dr. Shweta Tikoo, a senior research author from the Centennial Research Institute (Immune Imaging Project), pointed out that in the fight against advanced melanoma, new treatment strategies can be developed using individual drugs or part of a combination treatment plan, which is a Unmet needs.