Exploring cellular plasticity and resistance mechanisms in lung cancer: Innovations and emerging therapies
Caiyu Jiang, Shenglong Xie, Kegang Jia, Gang Feng, Xudong Ren, Youyu Wang
Abstract
Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer cases and remains the leading cause of cancer-related mortality worldwide. Firstly, this review explores the limitations of conventional therapies—chemotherapy, radiotherapy, and surgery—focusing on the development of drug resistance and significant toxicity that often hinder their efficacy. Thereafter, advancements in targeted therapies, such as immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs), are discussed, highlighting their impact on improving outcomes for patients with specific genetic mutations, including c-ros oncogene 1 receptor tyrosine kinase (ROS1), anaplastic lymphoma kinase (ALK), and epidermal growth factor receptor (EGFR). Additionally, the emergence of novel immunotherapies and phytochemicals is examined, emphasizing their potential to overcome therapeutic resistance, particularly in advanced-stage diseases. The review also delves into the role of next-generation sequencing (NGS) in enabling personalized treatment approaches and explores the clinical potential of innovative agents, such as bispecific T-cell engagers (BiTEs) and antibody-drug conjugates (ADCs). Finally, we address the socioeconomic barriers that limit the accessibility of these therapies in low-resource settings and propose future research directions aimed at improving the long-term efficacy and accessibility of these treatments. • A comprehensive review of lung cancer therapies, including chemotherapy, targeted therapy, and immunotherapy. • In-depth exploration of drug resistance mechanisms, cellular plasticity, and critical signaling pathways (EGFR, ALK, ROS1). • Summary of emerging therapies, including antibody-drug conjugates (ADCs) and phytochemicals, to address drug resistance. • Emphasis on the role of next-generation sequencing (NGS) and molecular profiling in advancing personalized treatment approaches for lung cancer.