Awaken "dormant" cells to fight cancer

   

   

Ten years ago, the advent of small molecule-targeted therapies revolutionized the treatment of metastatic melanoma, provided that tumors carry mutations
that respond to these therapies.
However, although a significant initial response can be seen in most patients, most patients relapse
even after a significant initial response.
These relapses are due to "dormant" persistent cells that do not respond
to treatment.
A team of researchers from the University of Geneva (UNIGE) and the University Hospital of Geneva (HUG) showed that these cells lacked the expression of a protein
called HuR.
By deciphering this underexpression mechanism, and by targeting an enzyme inhibitor, the team succeeded in reducing treatment resistance
in all melanoma cells.
These results, published in the Biochemical and Biophysical Research Newsletter, open up new avenues of treatment for metastatic melanoma and other types of solid cancer
.

Melanoma is one of the most dangerous skin cancers
.

Over the past decade, thanks to the advent of so-called small-molecule targeted therapies — drugs that can suppress a precise mechanism inside tumors to fight it — half of metastatic melanoma can be effectively treated, and sometimes even eradicated
.

A protein that regulates cell division is involved

This phenomenon is known as "adaptive resistance": certain cancer cells adapt to the drugs used to fight them and cause the disease to recur
.

Previous studies have shown that in slow-proliferating cells, a protein that regulates the expression of many genes that control cell division, the HuR protein, is underexpressed
.

Inhibit the enzyme to prevent recurrence

"In cells, messenger RNAs play a central role
in protein production.

"The biggest difficulty in carrying out this work is to study such cells because they are small in number and the state of underexpression of HuR protein is dynamic and reversible for any cell, making it difficult to detect and analyze; That is, at any time, the same cells can begin to proliferate and flip to a state
of high expression of this protein.

For the researchers and his team, "the next step will be to encourage the pharmaceutical industry to optimize inhibitors of recognized kinases to improve their stability and bioavailability, which is something that pharmaceutical companies now know how to do in a very systematic way, at least for such goals," Rastine Melat concluded
.

essay

Inhibition of the DAPKs-L13a axis prevents a GAIT-like motif-mediated HuR insufficiency in melanoma cells