How Cancer Cells Resist Chemotherapy: Design and Development of Drugs Targeting Protein-Protein Interactions

Abstract

Background: Resistance toward chemotherapeutics is one of the main obstacles on the way to effective cancer treatment. Personalization of chemotherapy could improve clinical outcome. However, despite preclinical significance, most of the potential markers have failed to reach clinical practice partially due to the inability of numerous studies to estimate the marker's impact on resistance properly.

Objective: The analysis of drug resistance mechanisms to chemotherapy in cancer cells, and the proposal of study design to identify bona fide markers.

Methods: A review of relevant papers in the field. A PubMed search with relevant keywords was used to gather the data. An example of a search request: drug resistance AND cancer AND paclitaxel.

Results: We have described a number of drug resistance mechanisms to various chemotherapeutics, as well as markers to underlie the phenomenon. We also proposed a model of a rational-designed study, which could be useful in determining the most promising potential biomarkers.

Conclusion: Taking into account the most reasonable biomarkers should dramatically improve clinical outcome by choosing the suitable treatment regimens. However, determining the leading biomarkers, as well as validating of the model, is a work for further investigations.

Keywords: Biomarkers; Cancer; Chemotherapy; Drug resistance; Oncological diseases; Protein-protein interaction..