Sep 2026· Current Drug Discovery Technologies· 0 citations
Medicine
TL;DR
This review encapsulates significant developments in molecularly targeted agents and immune checkpoint inhibitors, emphasising their clinical efficacy, resistance mechanisms, and innovative therapeutic combinations, and reviews pivotal clinical trials and newly filed patents.
Abstract
Lung cancer continues to be the foremost cause of cancer-related mortality globally, with non-small cell lung cancer (NSCLC) accounting for nearly 85% of cases. Historically, the prognosis for NSCLC was grim, but advancements in targeted therapies and immunotherapy are transforming treatment paradigms. This review encapsulates significant developments in molecularly targeted agents and immune checkpoint inhibitors, emphasising their clinical efficacy, resistance mechanisms, and innovative therapeutic combinations. A thorough literature search was conducted across PubMed, ClinicalTrials.gov, and other global intellectual property databases to highlight pivotal advancements in lung cancer therapies. Each section focuses on therapies targeting key molecular drivers such as Epidermal Growth Factor Receptor (EGFR), Anaplastic Lymphoma Kinase (ALK), and others, alongside immunotherapies targeting critical pathways like PD-1 and PD-L1. In genetically defined NSCLC subsets, targeted therapies such as Osimertinib and Lorlatinib have significantly enhanced progression-free survival. Similarly, immune checkpoint inhibitors like Nivolumab have redefined care standards, particularly in PD-L1-positive tumours. Nevertheless, challenges such as acquired resistance persist, prompting ongoing exploration of combination strategies and next-generation agents. This article also reviews pivotal clinical trials and newly filed patents, reflecting current and emerging commercial interests. The integration of molecular diagnostics and precision therapies is reshaping lung cancer treatment, with prospective directions aiming to overcome resistance and broaden access to innovative therapies worldwide, including from India and other developing regions.
Recent advances in NSCLC with established alterations are summarized, including EGFR, ALK, ROS1, KRAS, BRAF, RET, HER2, MET, and NTRK, and emerging targets are discussed, and emerging targets, such as NRG1 fusions, MTAP loss, and SMARCA4 deficiency are discussed.
L. Hendriks, Jessica J. Lin, D. S. Tan et al.· The Lancet Respiratory Medic...· 2 citations
This review summarizes established and emerging ICI-based regimens in lung cancer, mechanisms of resistance relevant to NSCLC and SCLC, biomarker integration for patient selection and monitoring, and future directions to optimize efficacy and safety through combinatory and alternative immunotherapeutic strategies.
Junyoung Park, Choong‐Hwan Kwak, Yu-Chan Chang et al.· Frontiers in Immunology· 0 citations
The rationale for targeting established and emerging antigens in non-small cell and small cell lung cancer, including HER2, TROP2, c-MET, HER3, CEACAM5, DLL3, and other promising targets currently under clinical investigation are discussed.
P. Paliogiannis, G. Fara, A. Zinellu et al.· Current Issues in Molecular...· 0 citations
The role of EGFRvIII in driving aggressive tumor growth is discussed and how effective targeting of EGFRvIII, and overcoming resistance mutations will be crucial to improve EGFR- and EGFRvIII-based therapies are highlighted.
U. Krishnaja, Neethu J, Maitheli Sarkar et al.· Immunotherapy· 0 citations
A major focus of this review is antibody-drug conjugates (ADCs) targeting novel surface antigens, including HER2, HER3, and TROP2, which have demonstrated remarkable clinical efficacy in EGFR TKI-resistant settings.
Xin-Ran Chen, Jia-Qi Liang, Jun-Kan Zhu et al.· Biochimica et biophysica act...· 0 citations
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