Awakening ‘dormant’ cells to fight cancer
Source: Science Daily, September 2022
The advent of small-molecule targeted therapies, a decade ago, revolutionized the treatment of metastatic melanoma, provided that the tumors carry the mutations to respond to these treatments. However, despite a remarkable initial response that can be seen in a majority of patients, most of them will undergo relapse even after spectacular initial responses. These relapses are due to “dormant" persistent cells, unresponsive to treatment. A team from the University of Geneva (UNIGE) and the University Hospitals of Geneva (HUG) has shown that these cells under-express a protein called HuR. By deciphering the mechanism of this insufficient expression and by targeting it with an enzyme inhibitor, this team has succeeded in reducing the therapeutic resistance of all melanoma cells. These results, published in Biochemical and Biophysical Research Communications, open new therapeutic avenues against metastatic melanoma and other types of solid cancers.
Melanoma is one of the most dangerous skin cancers. Potentially very aggressive, it develops from melanocytes, the cells responsible for skin pigmentation. The initial tumor can be superficial with a good prognosis upon removal, it can also be deeper and become metastatic, i.e. migrate to other organs in the body.
For the last ten years, thanks to the advent of the so-called small-molecule targeted therapies — drugs that inhibit a precise mechanism within the tumor to fight it — half of the metastatic melanomas that carry a genetic signature making them sensitive to these drugs, can be treated effectively, sometimes even be eradicated. “However, despite such spectacular initial responses, 80% of patients will suffer recurrences, and these recurrences will often occur in the same initially affected sites," explains Rastine Merat, researcher in the Department of Medicine at the UNIGE Faculty of Medicine and head of the Onco-dermatology Unit at the HUG.