Evidence mapPaperPMID 40322930Full record

ReviewCancer medicine2025

Strategies Beyond 3rd EGFR-TKI Acquired Resistance: Opportunities and Challenges.

Xuexue Zhou, Liang Zeng, Zhe Huang, Zhaohui Ruan, Huan Yan, Chun Zou, Shidong Xu, Yongchang Zhang

Abstract readReview
In one paragraph

Review in Cancer medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Article
  5. JIN-A02, a Mutant-Selective Fourth-Generation EGFR Inhibitor, Overcomes C797S-Mediated Resistance and Demonstrates Intracranial Activity in NSCLC.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
  6. Article
  7. Review
  8. Calcium Phosphate Nanoparticle Delivery of siInternational journal of nanomedicine · 2026
    Article
  9. Review
  10. Review
  11. Review
  12. Recent Advances in the Use ofPharmaceutics · 2025
    Review
  13. Article
  14. Article
  15. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Xuexue ZhouMedical College, Jishou University, Jishou, China.
Liang ZengDepartment of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
Zhe HuangDepartment of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
Zhaohui RuanDepartment of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
Huan YanDepartment of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
Chun ZouDepartment of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
Shidong XuDepartment of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
Yongchang ZhangMedical College, Jishou University, Jishou, China.ORCID https://orcid.org/0000-0002-6829-7176

Funding

National Natural Science Foundation of China 82173338National Natural Science Foundation of China 82222048National Natural Science Foundation of Hunan Province, China 2023JJ30368
6 · The paper itself

Abstract

The seminal identification of epidermal growth factor receptor (EGFR) mutations as pivotal oncogenic drivers in non-small cell lung cancer (NSCLC) has catalyzed the evolution of biomarker-guided therapeutic paradigms for advanced disease. Currently, third-generation EGFR tyrosine kinase inhibitors (EGFR-TKI) have revolutionized first-line treatment for advanced EGFR-mutated NSCLC, yet acquired resistance remains an inevitable and formidable clinical challenge. This review systematically summarizes molecular mechanisms underlying treatment resistance, with a focus on clinical challenges associated with central nervous system (CNS) metastases. Therapeutic resistance mechanisms are categorized into EGFR-dependent (on-target) pathways, typified by acquired kinase domain mutations (e.g., C797S), and EGFR-independent (off-target) pathways, involving compensatory activation of parallel signaling effectors (e.g., MET amplification, HER2 activation) or phenotypic transformation. We further evaluated contemporary diagnostic modalities for identifying resistance drivers and appraised emerging therapeutic strategies, including fourth-generation EGFR-TKI, various combination therapies, and antibody-drug conjugates (ADCs), and so forth, with emphasis on ongoing clinical trials that may transform the existing treatment paradigm. By synthesizing preclinical and clinical insights, this review aims to advance mechanistic understanding and propose therapeutic strategies to overcome acquired resistance to third-generation EGFR-TKI in first-line treatment.

Indexed as

Carcinoma, Non-Small-Cell LungDrug Resistance, NeoplasmLung NeoplasmsProtein Kinase InhibitorsErbB ReceptorsHumansMutationEGFR protein, humanErbB ReceptorsProtein Kinase Inhibitorsacquired resistance mechanismsEGFR mutationNSCLCtherapeutic strategiesthird‐generation EGFR‐TKI

Identifiers

PMID40322930
PMCPMC12051098

What Socratic holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.