Therapeutic strategy to stop melanoma spread

Monday, 10 February, 2020

Therapeutic strategy to stop melanoma spread

Scientists from Sydney’s Centenary Institute have developed a new therapeutic strategy that could potentially help the fight against advanced-stage melanoma, effectively reducing the migration and invasive properties of melanoma cells.

Described in the Journal of Investigative Dermatology, the team’s breakthrough was achieved by successfully inhibiting the interaction between two proteins involved in intracellular trafficking (the process by which molecules cross the membranes of living cells). The research is significant as metastasis — the process by which cancer moves to new areas of the body — is the leading cause of death in melanoma patients.

The researchers first found that high expression of the protein melanophilin was indicative of poor prognosis in melanoma patients. Employing human melanoma cell line models, the researchers were then able to demonstrate a significant reduction in the spread of cancer by blocking the ability of melanophilin to bind with the protein RAB27A — one of the critical regulators of intracellular transport.

“We have known for some time that the proteins melanophilin and RAB27A bind together and that this process could be crucial to help melanoma cells spread around the body,” said Centenary Institute PhD researcher Dajiang Guo, lead author of the study.

“By disrupting the binding of these two proteins with a recently developed blocking compound (BMD-20), we were able to successfully restrict the melanoma cell movement and invasion. What our findings suggest is that the development of new drugs that can specifically target melanophilin–RAB27A interactions are a promising target for advanced melanoma treatment.”

Dr Shweta Tikoo and PhD researcher Dajiang Guo. Image credit: Centenary Institute.

Senior study author Dr Shweta Tikoo added that there is an unmet need for novel therapeutic strategies that can be developed as a standalone drug or as part of a combination therapeutic regimen in the battle against advanced melanoma.

“Although we have witnessed a surge in new treatment options for advanced melanoma patients, especially involving immunotherapy (treatment that boosts the body’s immune system to fight cancer), issues such as limited effectiveness, drug resistance and drug toxicity persist,” Dr Tikoo said.

“Understanding and targeting the actual mechanisms underpinning melanoma progression and invasion is, therefore, vital for the development of new treatment strategies. Our findings have the potential to make a real difference in our battle against this devastating disease.”

Image credit: ©

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