Reactive Oxygen Species Reduction is a Key Underlying Mechanism of Drug Resistance in Cancer Chemotherapy

Amit K Maiti

doi:10.4172/2167-7700.1000104

Abstract

Reactive Oxygen Species (ROS) management in cancer cells is important for developing successful therapy. Most of the anticancer agents induce ROS generation to kill cancer cells by apoptosis through common molecular pathways. But prolonged treatment with the drug reduces ROS level to confer resistance. Subsequently, drug resistant cells have lower ROS content than drug sensitive cancer cells. Anticancer drugs induce master regulatory genes and these genes act on NFE2L2-KEAP1 antioxidant system to reduce the ROS level in cancer cells. This review focused on the genetic mechanism of drug mediated induction of ROS generation in sensitive cells and the ROS reduction in drug resistant cancer cells.

Highlights

Drug resistance is a devastating problem in cancer chemotherapy because drug resistant cancer cells are harder to kill with the same drug
Despite initial high response rate, a large proportion of patients develop resistance to the drug causing relapse of the disease. This multifaceted problem could be attributed to various factors, mainly on MDR (Multiple Drug Resistance) activation, tissue heterogeneity, microenvironmental context, abnormal mitochondrial respiration, vascularization, DNA repair and apoptosis [1]
Reactive oxygen species (ROS) with highly reactive oxygen atom reacts with DNA, amino acids of proteins and unsaturated fatty acids leading to oxidation of these biomolecules

Summary

Introduction

Drug resistance is a devastating problem in cancer chemotherapy because drug resistant cancer cells are harder to kill with the same drug. An alternative hypothesis suggests that oncogenes increase NFE2L2 (NRF2) expression to activate the antioxidant system for reducing ROS and detoxifying cells to induce tumorigenesis in mice [9]. Any cells, including cancer cells are vulnerable to excess ROS, somatic mutations in NFE2L2 or KEAP1 genes observed in cancer cells activate antioxidant systems to reduce the ROS level that helps tumor progression, but may not initiate tumor development.

Results

Conclusion