New class of drugs shows promise against BRAF-inhibitor-resistant melanoma
June 3, 2016
Researchers from Nice, France, have tested a new class of drugs—thiazole benzensulfonamides or TZBs—in melanoma and are getting promising results on biopsy samples from patients who are sensitive or resistant to BRAF inhibitor drugs.
Reporting their findings in Cancer Cell (online ahead of print May 26, 2016), the investigators from Inserm (Institut national de la santé et de la recherche médicale), explain how they developed a series of TZBs that produce stress on the endoplasmic reticulum of cancer cells resulting in cell death through induction of autophagic and apoptotic mechanisms.
TZBs were initially identified in research surrounding type 2 diabetes, as they increase the sensitivity of cells to insulin, but this trait would be counterproductive in a cancer therapy, the Inserm researchers note in a press release.
“If we wanted to use it against cancer, we had to be able to eliminate this proinsulin activity,” Inserm research director Stéphane Rocchi, PhD, said in the release. “Thus we started to modify its structure.”
The most promising of the TZBs, HA15, showed anti-cancer activity against cultured biopsies and mouse xenografts, including both those sensitive to and resistant to BRAF inhibitors. In the xeografts, HA15 reduced tumour volumes while not showing any toxic effects on normal cells.
Activity against other solid and liquid tumours, including breast, colon, prostate, pancreas, gliomas, and chronic myeloid leukemia, was also seen.
“The ultimate goal of this project is to use these new compounds in the treatment of melanoma and more generally in other types of cancers,” Dr. Rocchi concluded.
Dr. Rocchi and his team hope to begin phase I clinical trials soon.