Drug Resistance
Corresponding author: [email protected]
Abstract
Drug resistance is one of the major barriers to achieving durable responses in cancer therapy. Although many anticancer agents can initially reduce tumor burden, a proportion of cancer cells may survive treatment and subsequently develop or select for characteristics that reduce their sensitivity to therapy. Drug resistance may be intrinsic, acquired, reversible, or associated with the emergence of multidrug-resistant populations. Its development is driven by a complex interaction of genetic alterations, epigenetic reprogramming, altered drug transport, enhanced drug metabolism, modification of therapeutic targets, dysregulation of cell-death pathways, activation of alternative signaling networks, cancer stem-cell properties, and protection provided by the tumor microenvironment. These mechanisms are particularly important in reproductive cancers, where resistance to endocrine therapy, chemotherapy, platinum compounds, PARP inhibitors, radiotherapy, and targeted agents can significantly limit therapeutic success. Recent advances in liquid biopsy, circulating tumor DNA, circulating microRNAs, multi-omics, single-cell analysis, nanotechnology, and artificial intelligence are providing new opportunities for earlier detection and prediction of resistance. Combination therapy, sequential treatment, drug repurposing, targeted therapy, epigenetic intervention, immunotherapy, and personalized treatment strategies are being investigated to prevent or reverse resistance. Nanotechnology may further improve intracellular drug delivery, facilitate co-delivery of therapeutic agents, and help bypass drug-efflux mechanisms. Artificial intelligence is also emerging as a useful tool for integrating genomic, transcriptomic, epigenomic, proteomic, imaging, and clinical data to predict treatment response and identify resistance-associated patterns. A better understanding of resistance as a dynamic and evolving process may support a shift from reactive treatment after therapeutic failure toward predictive, biomarker-guided, and personalized cancer management.
Author Affiliations
- 1 Students, Department of Pharmaceutical Science, Ravindra Vidya Prasarak Mandal Institute of Pharmacy, Dwarka, Nashik, Maharashtra, India.