The Val d'Hebron Research Institute (VHIR) and the Autonomous University of Barcelona (UAB) have succeeded in deciphering a new mechanism to sensitize cancer cells to a specific treatment that has been ineffective so far due to tumor resistance.
In recent years, many anticancer treatments have been studied that have not been able to reach clinical practice. This is the case of TRAIL molecules, which, despite achieving good results in the preclinical stages, did not show the expected efficacy in clinical trials due to resistance of cancer cells. This research revealed the molecular mechanism by which cells become resistant to the antitumor action of TRAIL.
The results were published in the journal Cell death and diseaseIt was carried out in collaboration with the Biomedical Research Group in Gynecology of VHIR, IRB Barcelona and the Hospital del Mar Research Institute.
Sergio Espinoza, a researcher at VHIR and UAB and first author of the study, noted that these treatments are “very promising,” since TRAIL receptors are mainly located on cancer cells, but not on healthy cells, and thus “will reduce side effects.” on other cells.
The present study shows that protein kinase ERK5 plays a relevant role. In previous studies, ERK5 has already been shown to be involved in cell proliferation and cancer survival. It is now thought that activation of this protein also confers resistance to treatments that cause cell death.
The results showed that inhibiting ERK5 with drugs restores the sensitivity of cells to antitumor therapies. Researchers suggest administering ERK5 inhibitors to improve the antitumor efficacy of TRAIL agonists. The inhibitors will also help boost the activity of natural killer (NK) cells, a type of immune cell that has a powerful anti-tumor effect, also partly due to activation of the TRAIL pathway.
To date, the analysis has been performed on cell lines from different types of solid tumors, such as prostate, lung, cervical, or neuroblastoma, and in 3D cultures or endometrial-derived organoids of cancer patients. In the future, the researchers hope to find new collaborations to conduct clinical trials, with the aim of testing ERK5 inhibitors in cancer patients.
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