Cancer resistance to chemotherapy – are all possibilities exhausted?



Chemotherapy still remains to be the most important anticancer drug treatment considering the amount of patients who has indications for and who benefit from it. Chemotherapy efficacy is limited by primary and acquired resistance.

In this paper the molecular mechanisms contributing to chemoresistance are reviewed. They include active efflux, alterations of drug metabolism, target modification. Moreover, tumors can utilize adaptive mechanisms, such as activation of prosurvival signaling pathways or programmed cell death evasion. Epigenetic changes and tumor microenvironment factors also play pivotal role in cancer drug tolerance. In some cases, treatment failure is attributed to the presence of cancer stem cells, which are intrinsically tolerant to any stress. Finally, it became obvious that tumor heterogeneity and evolutionary dynamics is the major source for chemoresistance.

Therefore, resistance to chemotherapy seems to be highly multilayered complex phenomenon and the approaches to study and to reverse it in order to enhance tumor control should be based on multiple principles of interfering with intracellular molecular mechanisms and the tumor ecosystem as a whole.