Predicting Anticancer Drug Resistance Mediated by Mutations

Abstract

Cancer drug resistance presents a challenge for precision medicine. Drug-resistant mutations are always emerging. In this study, we explored the relationship between drug-resistant mutations and drug resistance from the perspective of protein structure. By combining data from previously identified drug-resistant mutations and information of protein structure and function, we used machine learning-based methods to build models to predict cancer drug resistance mutations. The performance of our combined model achieved an accuracy of 86%, a Matthews correlation coefficient score of 0.57, and an F1 score of 0.66. We have constructed a fast, reliable method that predicts and investigates cancer drug resistance in a protein structure. Nonetheless, more information is needed concerning drug resistance and, in particular, clarification is needed about the relationships between the drug and the drug resistance mutations in proteins. Highly accurate predictions regarding drug resistance mutations can be helpful for developing new strategies with personalized cancer treatments. Our novel concept, which combines protein structure information, has the potential to elucidate physiological mechanisms of cancer drug resistance.

Cancer Drugs and Target Prediction in Human. Minireview

“…However, the good news is that most normal cells are capable of recovering from the effects of chemo over time, a situation, which does not prevail in cancer cells, since they are mutated cells. These kind of cells are incapable to recover from the effects of chemo; hence, constituting advantage in the use of chemo to attack many types of cancer cells [9].…”