Scientists at the National Center for Cancer Research (CNIO) have discovered the weak spot that makes some tumors vulnerable to many drugs and multi-resistant, and devised a potential strategy to overcome it.

As the CNIO highlighted in a press release today, one of the biggest challenges in cancer is understanding why patients do not respond to treatment, because in some cases tumors exhibit multiple resistance, which significantly limits therapeutic options for patients. .

Researchers from the National Center for Cancer Research (CNIO) discovered one of the causes of this drug resistance in a study based primarily on cell lines, thus still far from clinical, and published in EMBO Molecular Medicine.

“Our result explains why many of the usual treatments don’t work for some tumors, and also identifies the weak points of these resistant cancers,” said Óscar Fernández-Capetillo, president of the CNIO Genomic Instability Group and lead author of the study. Research.

As the study shows, mutations that disable the function of a particular gene (FBXW7) “reduce susceptibility to the vast majority of current treatments”—the authors write—and also make tumor cells vulnerable to the action of a particular type of drug. : those that activate the “integrated stress response” (ISR).

The authors noted that this gene is one of the 10 most frequently mutated genes in human cancers and is associated with poor survival in all of them.

When the CNIO managed to link deficiency of this gene to multidrug resistance, they looked for the cause and found the answer in mitochondria, cell organelles involved in metabolism and cellular respiration.

The authors caution that this study, which adds to other recent studies, that activating the “integrated stress response” (ISR) may be a way to overcome resistance to chemotherapy, but they stressed: “There’s still a lot to do.”

And in that sense, they underlined the importance of continuing research to determine which drugs are best and most activating this response and which patients would benefit most from this strategy.

As reported by CNIO, the work received funding from the Ministry of Science and Innovation, the Spanish Association for the Fight Against Cancer (AECC), and the “La Caixa” Foundation, among others.