They find a mechanism used by cancer cells to evade chemotherapy

It is essential to deepen the knowledge of the mechanisms of resistance to antitumor therapies in order to improve the efficacy of treatments.

The group led by Francisco José Iborra at the Mixed Research Unit of the Institute of Biomedicine of Valencia (IBV), of the Higher Council for Scientific Research (CSIC) and the Príncipe Felipe Research Center (CIPF), in Spain, studies these mechanisms of resistance to cancer therapies using cell lines derived from human tumors, which are subjected to treatments and in which they study the changes that have occurred in resistant cells.

“In this study we have found that a mechanism that cells use to evade chemotherapy is a consequence of the stress response that chemotherapy induces,” explains Iborra. This reaction triggers the degradation of proteins, which causes the concentration of their basic components (amino acids) to increase within the cell, inducing, in turn, protein synthesis.

As a final result, the cell reduces its size and protein turnover increases. “This last point is very important, since a high protein turnover is necessary for cell plasticity, since cells must respond by changing their phenotype,” says the researcher.

Increase the effectiveness of chemotherapy

This study represents an important step, since it opens the possibility of designing more targeted and effective combination therapies for the treatment of cancer and, therefore, improving current treatments, increasing survival and the quality of life of patients. “We will be able to design therapies with protein synthesis inhibitors, or proteasome or autophagy inhibitors, which will make it possible to increase the efficacy of chemotherapy,” says the CSIC researcher.

“In our laboratory we have studied this possibility and we have observed that these combinations exert a positive synergistic effect, which suggests that this strategy could be useful for the treatment of tumors resistant to chemotherapy”, highlights the scientist. “But before going to the clinical field, we must test these combinations in animal models”, he remarks.

Image of a skin cancer where the expression of the glucose transporter (Glut1) is seen in green, the protein pyruvate kinase 2 (PKM2) in red and the DNA in blue. (Image: IBV / CIPF)

This research has been carried out in the CIPF laboratories in Valencia, using cultured tumor cell lines of various types of tumors and computational modelling. The research has been carried out in collaboration with the CSIC’s National Center for Biotechnology (CNB), the Hospital del Vinalopó (Elche, Spain) and the University of Helsinki (Finland).

The study is titled “Chemotherapy induces cell plasticity; controlling plasticity increases therapeutic response”. And it has been published in the academic journal Signal Transduction and Targeted Therapy. (Source: CSIC)