Triple blow to the tumor
Pushchina scientists have shown the need for a comprehensive solution to three key problems of oncology to improve the effectiveness of therapy
Polina Kirsanova, ITEB RAS Press Service
Pushchina scientists have shown the need for a comprehensive solution to three key problems of oncology to improve the effectiveness of clinical therapy. It is well known that the treatment of oncological diseases is one of the most urgent tasks of modern medicine. The effectiveness of treatment is greatly hampered due to the heterogeneity of the properties of cells in the tumor. For example, in one tumor, cells can grow at completely different rates or be more or less resistant to drugs, etc. To develop effective drugs, three key problems of oncology must be taken into account:
selectivity of drugs – it is necessary to develop drugs that destroy only cancer cells and do not damage healthy ones; resistance (resistance) of tumor cells to drugs – most of the malignant cells become resistant to drugs due to the fact that malignant cells grow faster than the blood vessels that feed them. This is how zones of oxygen deficiency – hypoxia arise, mutations increase, various mechanisms of cell protection are activated, including those associated with intercellular interactions; restriction of the penetration of drugs to tumor cells deep into the tissue, which is especially characteristic of high-molecular substances, for example, antibodies.
Scientists from the Laboratory of Pharmacological Regulation of Cell Resistance and the Laboratory of Tissue Engineering of the ITEB RAS, in collaboration with specialists from the Herzen Moscow Cancer Research Institute, assessed the need for a comprehensive solution to all three of the above problems to increase the effectiveness of the antitumor recombinant protein izTRAIL. The results of the study are published in the February issue of the International Journal of Molecular Sciences (Fadeev et al., Improved Anticancer Effect of Recombinant Protein izTRAIL Combined with Sorafenib and Peptide).
Schematic representation of the experiment (provided by the authors).
TRAIL is a natural anti–cancer protein that can cause the death of only tumor cells without damaging healthy ones. It showed high efficiency in experiments on cells outside the body, but was not effective in preclinical trials. The authors of the work suggested that this is due to the acquisition of drug resistance of tumor cells in the body and with the restriction of protein penetration into tumor tissue. To suppress the resistance to the izTRAIL protein of human tumor cells injected into immunodeficient mice, the scientists added the antitumor drug sorafenib (in non-toxic concentrations), which, as they have previously shown, is able to suppress the resistance of cells to the izTRAIL protein. This partially suppressed the growth of the tumor. To further enhance the antitumor effect, the researchers used a special peptide iRGD, consisting of 9 amino acids and capable of enhancing the penetration of drugs into tumor tissue. As a result of this experiment, it was found that the most significant increase in the antitumor effect of the TRAIL protein is observed only when it is combined with sorafenib and the iRGD peptide.
"Our results indicate the need for a comprehensive solution to all key problems of oncology for effective antitumor therapy, including the need for selectivity of drugs in relation to tumor cells, increased drug resistance of tumor cells at a distance from blood vessels and limiting the penetration of drugs deep into the tumor tissue," one of the authors of the study, head of the laboratory, told the press service of ITEB RAS pharmacological regulation of cell resistance, Candidate of Biological Sciences, Roman Sergeevich Fadeev.
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