Understanding the Mechanisms of Drug Resistance in Non-Small Cell Lung Cancer Potential Therapeutic Approaches

Background: Drug resistance is a major obstacle to the successful treatment of non-small cell lung cancer (NSCLC), the most common subtype of lung cancer. The purpose of this research was to look at possible treatment approaches and the processes behind drug resistance in non-small cell lung cancer. Methods: From March 2022 to February 2024, a prospective observational research was carried out at Lady Reading Hospital in Peshawar. 128 NSCLC patients in all were enrolled. Next-generation sequencing, DNA methylation tests, and immunological profiling were used to examine the genetic, epigenetic, and environmental components linked to medication resistance. Multivariate logistic regression, t-tests, chi-square tests, and Kaplan-Meier survival analysis were among the statistical techniques used. Results: T790M mutations contributed to resistance, with EGFR mutations found in 35% of patients. Ten percent of patients had MET amplifications, while seven percent of patients had ALK rearrangements. In resistant cancers, epigenetic changes such as hypoacetylation of histones and hypermethylation of CDKN2A were common. Immunosuppressive cells and cancer-associated fibroblasts were abundant in the tumor microenvironment. The median overall survival (OS) of patients with drug-resistant NSCLC was 14 months, a substantial decrease from the 22 months seen in patients without resistance (p < 0.001). Conclusions: The research emphasizes how genetic, epigenetic, and microenvironmental variables all play a role in the complex process of medication resistance in non-small cell lung cancer. Molecular profiling and targeted medicines along with personalized treatment techniques are critical to overcome resistance and enhancing patient outcomes. Larger, more varied populations and the creation of cutting-edge treatment approaches should be the main topics of future study.