In a recent study published in the journal Cancer Cell scientists at The Institute of Cancer Research, London, and the Cancer Research UK Manchester Institute, found a new family of drugs, panRAF inhibitors, which can be efficiently used to treat melanoma patients who developed resistance to BRAF inhibitors.
Currently, several melanoma drugs specifically target proteins derived from genetic BRAF mutations present in roughly 50% of all melanomas. However, while in the beginning these drugs prove effective, many patients develop some degree of resistance within the first year of treatment.
In this study, the team demonstrated that two panRAF inhibitors, CCT196969 and CCT241161, were able to stop the development of BRAF-driven melanomas, even if these cancers had already gained resistance to BRAF-inhibitors.
Importantly, these novel compounds were able to stop tumor progression in cancers that were never responsive to BRAF inhibitors, a situation that accounts for about 20% of all melanoma cases.
“Melanomas often respond initially to the current generation of treatments, but they inevitably acquire resistance to them, and there is a desperate need for more effective options. Our new inhibitors are the first in a new family of drugs that attack cancers without allowing them the get-out clause of drug resistance, by blocking multiple cancer proteins at once. We are very hopeful that clinical trials from this series of new inhibitors will begin very soon — and that they will ultimately become new first or second-line options for patients who, at the moment, exhaust all the available treatments and end up with fatal disease”, study co-author Professor Caroline Springer, Professor of Biological Chemistry at The Institute of Cancer Research, London said in a press release.
The mechanism of action behind these new drugs seems to be their capacity to simultaneously target BRAF and the growth pathways that cancer cells depend upon when they become resistant.
The research team used animal models of melanoma to test the novel compounds along with drug-resistant tumors taken from patients and implanted into mice.
Study co-author Professor Richard Marais, Director of the Cancer Research UK Manchester Institute, based at The University of Manchester, further added, “Our laboratory study showed that these new drugs deliver multiple blows to cancer by hitting several cell survival routes at once. It’s a step on from the drugs that are currently available which can’t multitask in this way. The next step is testing this family of drugs in clinical trials to establish that they are both safe and effective in cancer patients, potentially providing urgently-needed new treatments for patients who have run out of options. The trial is set to open soon and we await the results with great interest.”
