Affiliation:
1. Department of Pharmacology, School of Pharmaceutical Sciences, Bhagwant University, Sikar Road, Ajmer, Rajasthan 305004, India.
2. Department of Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, United States.
Abstract
Drug resistance poses a significant challenge in cancer therapy, limiting the effectiveness of various treatment modalities and adversely impacting patient outcomes. This review article aims to provide a comprehensive overview of the mechanisms underlying drug resistance in cancer and the associated challenges. We discuss the intrinsic and acquired mechanisms of drug resistance, including genetic alterations, tumor heterogeneity, cellular plasticity, drug efflux pumps, DNA repair mechanisms, and bypass signaling pathways. Additionally, we explore the challenges posed by the tumor microenvironment, cancer stem cells, and the emergence of resistance during treatment. Furthermore, we highlight the strategies employed to overcome drug resistance, including combination therapies, targeted therapies, immunotherapy, nanomedicine, and the potential of precision medicine and biomarker-guided approaches. Finally, we present recent examples and advancements in understanding and overcoming drug resistance in cancer therapy, highlighting the latest research findings and therapeutic approaches.