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Emerging Targeted Therapies and Evolving Treatment Paradigms in Non-Small Cell...
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Emerging Targeted Therapies and Evolving Treatment Paradigms in Non-Small Cell Lung Cancer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 31 October 2026 | Viewed by 1159

Special Issue Editor

Dr. Luis E. Raez

E-Mail Website
Guest Editor
Memorial Cancer Institute, Memorial Healthcare System, Pembroke Pines, FL 33026, USA
Interests: non-small cell lung cancer (NSCLC); molecular profiling; precision medicine; circulating tumor DNA (ctDNA); cancer therapy

Special Issue Information

Dear Colleagues,

During 2024 and 2025 several new targeted therapies have been FDA approved for NSCLC and several more are coming in 2026. In this special issue we want to review not only the latest approvals in targeted therapy but also some of the agents that are not as popular or well know as others. For example Her2 therapy or MET amplification therapy in lung cancer have had a major boost in the last two years with the approvals or zongertinib or Telisotuzumab vedotin and more agents are coming in these fields. We will review mechanisms of action, efficacy and toxicity management of several of these new agents. Also current indications and near future potential indications in the management of NSCLC.

Dr. Luis E. Raez
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • non-small cell lung cancer (NSCLC)
  • targeted therapies
  • human epidermal growth factor receptor 2 (HER2)
  • mesenchymal-epithelial transition factor (MET)
  • anaplastic lymphoma kinase (ALK)
  • C-ROS oncogene 1 receptor tyrosine kinase (ROS1)
  • rearranged during transfection (RET)
  • neurotrophic tyrosine receptor kinase (NTRK)
  • B-Raf proto-oncogene serine/threonine kinase V600 mutation (BRAFv600)
  • Kirsten rat sarcoma viral oncogene homolog (KRAS)
  • epidermal growth factor receptor (EGFR)

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Published Papers (1 paper)

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Review

23 pages, 2401 KB  
Review
Therapeutic Advances in Non-Small Cell Lung Cancer Harboring EGFR Exon 20 Insertion Mutations: From Molecular Biology to Targeted Therapy
by Daniel Rosas, Jay Desai and Luis Raez
Int. J. Mol. Sci. 2026, 27(9), 3714; https://doi.org/10.3390/ijms27093714 - 22 Apr 2026
Viewed by 845
Abstract
Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations are the third most common EGFR mutation subtype in non-small cell lung cancer (NSCLC), accounting for approximately 4–12% of all EGFR-mutated cases. Unlike classical EGFR mutations, ex20ins mutations confer inherent [...] Read more.
Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations are the third most common EGFR mutation subtype in non-small cell lung cancer (NSCLC), accounting for approximately 4–12% of all EGFR-mutated cases. Unlike classical EGFR mutations, ex20ins mutations confer inherent resistance to first-, second- and third-generation EGFR tyrosine kinase inhibitors (TKIs) due to unique structural alterations that lock the αC-helix in an active orientation, creating steric hindrance within the drug-binding pocket. Until recently, platinum-based chemotherapy remained the standard first-line treatment, with objective response rates (ORR) of 19–47% and a median progression-free survival (PFS) of 6–7 months. Over the past five years, the therapeutic landscape has shifted, driven by the development of selective inhibitors and bispecific antibodies. Amivantamab, a bispecific EGFR–mesenchymal–epithelial transition factor (MET) antibody combined with chemotherapy, demonstrated superior efficacy in the PAPILLON trial, with an ORR of 73% and a median PFS of 11.4 months in the first-line setting. Sunvozertinib, an oral, selective EGFR inhibitor, received U.S. Food and Drug Administration (FDA) accelerated approval in 2025, with an ORR of 46% and a median duration of response (DOR) of 11.1 months in platinum-pretreated patients. Emerging therapies, including zipalertinib and furmonertinib, have shown promising results in early-phase trials, with zipalertinib demonstrating activity in patients pretreated with amivantamab (ORR 31.5%) and furmonertinib achieving remarkable responses in treatment-naive patients (ORR 78.6% at 240 mg). This comprehensive review analyzes the molecular biology, structural mechanisms, current therapeutic options, and novel investigational agents for EGFR ex20ins-mutated NSCLC. Full article
(This article belongs to the Special Issue Emerging Targeted Therapies and Evolving Treatment Paradigms in Non-Small Cell Lung Cancer)
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