Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
October-2026 Volume 56 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
October-2026 Volume 56 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review Open Access

Genomic instability, postoperative recurrence and therapeutic vulnerabilities in resectable non‑small cell lung cancer (Review)

  • Authors:
    • Linlin Wang
    • Yong Feng
    • Qiang Liu
  • View Affiliations / Copyright

    Affiliations: Department of Thoracic Surgery, Shenyang Tenth People's Hospital, Shenyang, Liaoning 110044, P.R. China, Oncology Department of Integrated Traditional Chinese and Western Medicine, Shenyang Tenth People's Hospital, Shenyang, Liaoning 110044, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 182
    |
    Published online on: August 28, 2026
       https://doi.org/10.3892/or.2026.9188
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:


Abstract

Resectable non‑small cell lung cancer (NSCLC) is managed largely according to anatomical stage, pathological risk and actionable driver alterations, yet these factors do not fully explain postoperative recurrence. Genomic instability may contribute to recurrence by promoting clonal diversification, intratumoral heterogeneity, occult dissemination, persistence of residual tumor cells, and immune escape. In the present review, chromosomal instability (CIN), copy‑number complexity, whole‑genome doubling, DNA repair defects, replication stress, and extrachromosomal DNA (ecDNA) were critically evaluated using a three‑axis translational framework encompassing biological consequences, potential clinical roles, and strength of evidence. Current evidence suggests that clonal diversity and copy‑number complexity have the clearest near‑term prognostic rationale. By contrast, CIN and whole‑genome doubling are supported more strongly by evolutionary and mechanistic rather than prospective clinical evidence. Defects in DNA repair, replication stress, and ecDNA represent potential therapeutic vulnerabilities, but their clinical relevance remains to be established. To date, no treatment‑predictive biomarkers based on genomic instability have been identified for resectable NSCLC. Direct clinical evidence linking any specific genomic instability feature to the presence or longitudinal dynamics of postoperative molecular residual disease (MRD) remains limited. Postoperative circulating tumor DNA‑defined MRD provides prognostic information more directly related to residual disease but remains assay‑dependent and should not be considered a genomic‑instability phenotype. Therefore, features of genomic instability should remain investigational and should not replace established clinical, pathological, or molecular decision‑making. Their near‑term value lies in refining biological risk models and generating testable hypotheses for biomarker‑defined perioperative trials.
View Figures

Figure 1

Proposed relationships among genomic
instability, clonal evolution, occult residual disease and
postoperative recurrence in resectable NSCLC. Genomic instability
may generate intratumoral diversity, from which microenvironmental
and therapeutic pressures may select subclones with survival or
dissemination advantages. These subclones may persist as dormant or
micrometastatic residual disease after complete resection and
contribute to recurrence. Postoperative ctDNA-defined MRD is an
assay-dependent signal rather than a direct measure of viable
residual tumor cells or their genomic instability. Direct evidence
linking specific instability features to postoperative MRD dynamics
remains limited. NSCLC, non-small cell lung cancer; ctDNA,
circulating tumor DNA; MRD, molecular residual disease; ATR, ataxia
telangiectasia and Rad3-related; DNA, deoxyribonucleic acid; ecDNA,
extrachromosomal DNA.

Figure 2

Genomic-instability-informed
perioperative precision framework for resectable NSCLC. Established
clinicopathological factors and validated molecular tests remain
the basis for perioperative management. Tissue-based genomic
instability profiling, longitudinal ctDNA-defined MRD assessment,
and immune characterization may provide complementary but
non-equivalent information on tumor evolution, residual disease
risk, and candidate vulnerabilities. These investigational layers
may support risk model development and biomarker-defined clinical
trials but should not replace validated treatment indications.
NSCLC, non-small cell lung cancer; ctDNA, circulating tumor DNA;
MRD, molecular residual disease; DDR, DNA damage response; STAS,
spread through air spaces; TNM, tumor-node-metastasis.
View References

1 

Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, et al: Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N Engl J Med. 386:1973–1985. 2022. View Article : Google Scholar : PubMed/NCBI

2 

Wakelee H, Liberman M, Kato T, Tsuboi M, Lee SH, Gao S, Chen KN, Dooms C, Majem M, Eigendorff E, et al: Perioperative pembrolizumab for Early-stage non-small-cell lung cancer. N Engl J Med. 389:491–503. 2023. View Article : Google Scholar : PubMed/NCBI

3 

Tsuboi M, Herbst RS, John T, Kato T, Majem M, Grohé C, Wang J, Goldman JW, Lu S, Su WC, et al: Overall survival with osimertinib in resected EGFR-Mutated NSCLC. N Engl J Med. 389:137–147. 2023. View Article : Google Scholar : PubMed/NCBI

4 

Felip E, Altorki N, Zhou C, Csőszi T, Vynnychenko I, Goloborodko O, Luft A, Akopov A, Martinez-Marti A, Kenmotsu H, et al: Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): A randomised, multicentre, open-label, phase 3 trial. Lancet. 398:1344–1357. 2021. View Article : Google Scholar : PubMed/NCBI

5 

Mountzios G, Remon J, Hendriks LEL, Garcia-Campelo R, Rolfo C, Van Schil P, Forde PM, Besse B, Subbiah V, Reck M, et al: Immune-checkpoint inhibition for resectable non-small-cell lung cancer-opportunities and challenges. Nat Rev Clin Oncol. 20:664–677. 2023. View Article : Google Scholar : PubMed/NCBI

6 

Frankell AM, Dietzen M, Al Bakir M, Lim EL, Karasaki T, Ward S, Veeriah S, Colliver E, Huebner A, Bunkum A, et al: The evolution of lung cancer and impact of subclonal selection in TRACERx. Nature. 616:525–533. 2023. View Article : Google Scholar : PubMed/NCBI

7 

Martínez-Ruiz C, Black JRM, Puttick C, Hill MS, Demeulemeester J, Larose Cadieux E, Thol K, Jones TP, Veeriah S, Naceur-Lombardelli C, et al: Genomic-transcriptomic evolution in lung cancer and metastasis. Nature. 616:543–552. 2023. View Article : Google Scholar : PubMed/NCBI

8 

Al Bakir M, Huebner A, Martínez-Ruiz C, Grigoriadis K, Watkins TBK, Pich O, Moore DA, Veeriah S, Ward S, Laycock J, et al: The evolution of non-small cell lung cancer metastases in TRACERx. Nature. 616:534–542. 2023. View Article : Google Scholar : PubMed/NCBI

9 

Black JRM, Bartha G, Abbott CW, Boyle SM, Karasaki T, Li B, Chen R, Harris J, Veeriah S, Colopi M, et al: Ultrasensitive ctDNA detection for preoperative disease stratification in early-stage lung adenocarcinoma. Nat Med. 31:70–76. 2025. View Article : Google Scholar : PubMed/NCBI

10 

Yap TA, Manning HC, Sapra P, Mills GB and O'Connor MJ: Targeting genomic instability in cancer. Cell. 189:2278–2306. 2026. View Article : Google Scholar : PubMed/NCBI

11 

Chen X, Agustinus AS, Li J, DiBona M and Bakhoum SF: Chromosomal instability as a driver of cancer progression. Nat Rev Genet. 26:31–46. 2025. View Article : Google Scholar : PubMed/NCBI

12 

Pawlik P, Grigoriadis K, Bunkum A, Coggan H, Frankell AM, Martínez-Ruiz C, Karasaki T, Huebner A, Rowan A, Fisher J, et al: Clone copy number diversity is linked to survival in lung cancer. Nature. 646:190–197. 2025. View Article : Google Scholar : PubMed/NCBI

13 

Lu WT, Zalmas LP, Bailey C, Black JRM, Martinez-Ruiz C, Pich O, Gimeno-Valiente F, Usaite I, Magness A, Thol K, et al: TRACERx analysis identifies a role for FAT1 in regulating chromosomal instability and whole-genome doubling via Hippo signalling. Nat Cell Biol. 27:154–168. 2025. View Article : Google Scholar : PubMed/NCBI

14 

Baker TM, Lai S, Lynch AR, Lesluyes T, Yan H, Ogilvie HA, Verfaillie A, Dentro S, Bowes AL, Pillay N, et al: The history of chromosomal instability in Genome-Doubled tumors. Cancer Discov. 14:1810–1822. 2024. View Article : Google Scholar : PubMed/NCBI

15 

Gimeno-Valiente F, Castignani C, Larose Cadieux E, Mensah NE, Liu X, Chen K, Chervova O, Karasaki T, Weeden CE, Richard C, et al: DNA methylation cooperates with genomic alterations during non-small cell lung cancer evolution. Nat Genet. 57:2226–2237. 2025. View Article : Google Scholar : PubMed/NCBI

16 

Tang J, Weiser NE, Wang G, Chowdhry S, Curtis EJ, Zhao Y, Wong ITL, Marinov GK, Li R, Hanoian P, et al: Enhancing transcription-replication conflict targets ecDNA-positive cancers. Nature. 635:210–218. 2024. View Article : Google Scholar : PubMed/NCBI

17 

Hopkins JL, Lan L and Zou L: DNA repair defects in cancer and therapeutic opportunities. Genes Dev. 36:278–293. 2022. View Article : Google Scholar : PubMed/NCBI

18 

Li Q, Qian W, Zhang Y, Hu L, Chen S and Xia Y: A new wave of innovations within the DNA damage response. Signal Transduct Target Ther. 8:3382023. View Article : Google Scholar : PubMed/NCBI

19 

Caswell DR, Gui P, Mayekar MK, Law EK, Pich O, Bailey C, Boumelha J, Kerr DL, Blakely CM, Manabe T, et al: The role of APOBEC3B in lung tumor evolution and targeted cancer therapy resistance. Nat Genet. 56:60–73. 2024. View Article : Google Scholar : PubMed/NCBI

20 

Díaz-Gay M, Zhang T, Hoang PH, Leduc C, Baine MK, Travis WD, Sholl LM, Joubert P, Khandekar A, Zhao W, et al: The mutagenic forces shaping the genomes of lung cancer in never smokers. Nature. 644:133–144. 2025. View Article : Google Scholar : PubMed/NCBI

21 

Zhang T, Sang J, Hoang PH, Zhao W, Rosenbaum J, Johnson KE, Klimczak LJ, McElderry J, Klein A, Wirth C, et al: APOBEC affects tumor evolution and age at onset of lung cancer in smokers. Nat Commun. 16:47112025. View Article : Google Scholar : PubMed/NCBI

22 

Everall A, Tapinos A, Hawari A, Cornish AJ, Sud A, Chubb D, Kinnersley B, Frangou A, Barquin M, Jung J, et al: Comprehensive repertoire of the chromosomal alteration and mutational signatures across 16 cancer types. Nat Genet. 58:570–581. 2026. View Article : Google Scholar : PubMed/NCBI

23 

Jamal-Hanjani M, Wilson GA, McGranahan N, Birkbak NJ, Watkins TBK, Veeriah S, Shafi S, Johnson DH, Mitter R, Rosenthal R, et al: Tracking the evolution of non-small-cell lung cancer. N Engl J Med. 376:2109–2121. 2017. View Article : Google Scholar : PubMed/NCBI

24 

Diossy M, Sztupinszki Z, Borcsok J, Krzystanek M, Tisza V, Spisak S, Rusz O, Timar J, Csabai I, Fillinger J, et al: A subset of lung cancer cases shows robust signs of homologous recombination deficiency associated genomic mutational signatures. NPJ Precis Oncol. 5:552021. View Article : Google Scholar : PubMed/NCBI

25 

Yan X, Mischel P and Chang H: Extrachromosomal DNA in cancer. Nat Rev Cancer. 24:261–273. 2024. View Article : Google Scholar : PubMed/NCBI

26 

De Zuani M, Xue H, Park JS, Dentro SC, Seferbekova Z, Tessier J, Curras-Alonso S, Hadjipanayis A, Athanasiadis EI, Gerstung M, et al: Single-cell and spatial transcriptomics analysis of non-small cell lung cancer. Nat Commun. 15:43882024. View Article : Google Scholar : PubMed/NCBI

27 

Lomakin A, Svedlund J, Strell C, Gataric M, Shmatko A, Rukhovich G, Park JS, Ju YS, Dentro S, Kleshchevnikov V, et al: Spatial genomics maps the structure, nature and evolution of cancer clones. Nature. 611:594–602. 2022. View Article : Google Scholar : PubMed/NCBI

28 

Hertel A, Streuer A, Diehl S, Boch T, Nörenberg D, Strittmatter A, Zöllner FG, Schoenberg SO, Hofmann WK, Loges S, et al: Targeting tumoral heterogeneity in lung cancer: A novel, CT-texture-guided targeted biopsy approach with exome sequencing. NPJ Precis Oncol. 9:3422025. View Article : Google Scholar : PubMed/NCBI

29 

Hessey S, Bunkum A, Huebner A, Haase K, Grigoriadis K, Naceur-Lombardelli C, Liu WK, Harrigan CF, Grieco C, Marinelli D, et al: Evolutionary characterization of lung cancer metastasis. Nature. 653:911–922. 2026. View Article : Google Scholar : PubMed/NCBI

30 

Enfield KSS, Colliver E, Lee C, Magness A, Moore DA, Sivakumar M, Grigoriadis K, Pich O, Karasaki T, Hobson PS, et al: Spatial architecture of myeloid and T cells orchestrates immune evasion and clinical outcome in lung cancer. Cancer Discov. 14:1018–1047. 2024. View Article : Google Scholar : PubMed/NCBI

31 

Mo CK, Liu J, Chen S, Storrs E, Targino da Costa ALN, Houston A, Wendl MC, Jayasinghe RG, Iglesia MD, Ma C, et al: Tumour evolution and microenvironment interactions in 2D and 3D space. Nature. 634:1178–1186. 2024. View Article : Google Scholar : PubMed/NCBI

32 

Gerstberger S, Jiang Q and Ganesh K: Metastasis. Cell. 186:1564–1579. 2023. View Article : Google Scholar : PubMed/NCBI

33 

Goddard ET, Linde MH, Srivastava S, Klug G, Shabaneh TB, Iannone S, Grzelak CA, Marsh S, Riggio AI, Shor RE, et al: Immune evasion of dormant disseminated tumor cells is due to their scarcity and can be overcome by T cell immunotherapies. Cancer Cell. 42:119–134.e12. 2024. View Article : Google Scholar : PubMed/NCBI

34 

Li Y, Liu F, Cai Q, Deng L, Ouyang Q, Zhang XHF and Zheng J: Invasion and metastasis in cancer: Molecular insights and therapeutic targets. Signal Transduct Target Ther. 10:572025. View Article : Google Scholar : PubMed/NCBI

35 

Dijkstra KK, Vendramin R, Karagianni D, Witsen M, Gálvez-Cancino F, Hill MS, Foster KA, Barbè V, Angelova M, Hynds RE, et al: Subclonal immune evasion in non-small cell lung cancer. Cancer Cell. 43:1833–1849.e10. 2025. View Article : Google Scholar : PubMed/NCBI

36 

Wang C, Li J, Chen J, Wang Z, Zhu G, Song L, Wu J, Li C, Qiu R, Chen X, et al: Multi-omics analyses reveal biological and clinical insights in recurrent stage I non-small cell lung cancer. Nat Commun. 16:14772025. View Article : Google Scholar : PubMed/NCBI

37 

Chemi F, Rothwell DG, McGranahan N, Gulati S, Abbosh C, Pearce SP, Zhou C, Wilson GA, Jamal-Hanjani M, Birkbak NJ, et al: Pulmonary venous circulating tumor cell dissemination before tumor resection and disease relapse. Nat Med. 25:1534–1539. 2019. View Article : Google Scholar : PubMed/NCBI

38 

Liang Y, Chen WM, Zhang Y and Li L: Remodeling the tumor dormancy ecosystem to prevent recurrence and metastasis. Signal Transduct Target Ther. 11:12026. View Article : Google Scholar : PubMed/NCBI

39 

Hong TH, Hwang S, Dasgupta A, Abbosh C, Hung T, Bredno J, Walker J, Shi X, Milenkova T, Horn L, et al: Clinical utility of Tumor-Naïve presurgical circulating tumor DNA detection in Early-stage NSCLC. J Thorac Oncol. 19:1512–1524. 2024. View Article : Google Scholar : PubMed/NCBI

40 

Gale D, Heider K, Ruiz-Valdepenas A, Hackinger S, Perry M, Marsico G, Rundell V, Wulff J, Sharma G, Knock H, et al: Residual ctDNA after treatment predicts early relapse in patients with early-stage non-small cell lung cancer. Ann Oncol. 33:500–510. 2022. View Article : Google Scholar : PubMed/NCBI

41 

Tran HT, Heeke S, Sujit SJ, Vokes N, Zhang J, Aminu M, Lam VK, Vaporciyan A, Swisher SG, Godoy MCB, et al: Circulating tumor DNA and radiological tumor volume identify patients at risk for relapse with resected, early-stage non-small-cell lung cancer. Ann Oncol. 35:183–189. 2024. View Article : Google Scholar : PubMed/NCBI

42 

Sujit SJ, Aminu M, Karpinets TV, Chen P, Saad MB, Salehjahromi M, Boom JD, Qayati M, George JM, Allen H, et al: Enhancing NSCLC recurrence prediction with PET/CT habitat imaging, ctDNA, and integrative radiogenomics-blood insights. Nat Commun. 15:31522024. View Article : Google Scholar : PubMed/NCBI

43 

Herbst RS, John T, Grohé C, Goldman JW, Kato T, Laktionov K, Bonanno L, Tiseo M, Majem M, Dómine M, et al: Molecular residual disease analysis of adjuvant osimertinib in resected EGFR-mutated stage IB-IIIA non-small-cell lung cancer. Nat Med. 31:1958–1968. 2025. View Article : Google Scholar : PubMed/NCBI

44 

Stetson D, Labrousse P, Russell H, Shera D, Abbosh C, Dougherty B, Barrett JC, Hodgson D and Hadfield J: Next-Generation molecular residual disease assays: Do we have the tools to evaluate them properly? J Clin Oncol. 42:2736–2740. 2024. View Article : Google Scholar : PubMed/NCBI

45 

Boukouris AE, Michaelidou K, Joosse SA, Charpidou A, Mavroudis D, Syrigos KN and Agelaki S: A comprehensive overview of minimal residual disease in the management of early-stage and locally advanced non-small cell lung cancer. NPJ Precis Oncol. 9:1782025. View Article : Google Scholar : PubMed/NCBI

46 

Moding EJ, Nabet BY, Alizadeh AA and Diehn M: Detecting liquid remnants of solid tumors: Circulating tumor DNA minimal residual disease. Cancer Discov. 11:2968–2986. 2021. View Article : Google Scholar : PubMed/NCBI

47 

Zheng J, Qin C, Wang Q, Tian D and Chen Z: Circulating tumour DNA-Based molecular residual disease detection in resectable cancers: A systematic review and meta-analysis. EBioMedicine. 103:1051092024. View Article : Google Scholar : PubMed/NCBI

48 

Venkatesan S, Angelova M, Puttick C, Zhai H, Caswell DR, Lu WT, Dietzen M, Galanos P, Evangelou K, Bellelli R, et al: Induction of APOBEC3 exacerbates DNA replication stress and chromosomal instability in early breast and lung cancer evolution. Cancer Discov. 11:2456–2473. 2021. View Article : Google Scholar : PubMed/NCBI

49 

Isozaki H, Sakhtemani R, Abbasi A, Nikpour N, Stanzione M, Oh S, Langenbucher A, Monroe S, Su W, Cabanos HF, et al: Therapy-induced APOBEC3A drives evolution of persistent cancer cells. Nature. 620:393–401. 2023. View Article : Google Scholar : PubMed/NCBI

50 

Wang X, Bai H, Zhang J, Wang Z, Duan J, Cai H, Cao Z, Lin Q, Ding X, Sun Y, et al: Genetic intratumor heterogeneity remodels the immune microenvironment and induces immune evasion in brain metastasis of lung cancer. J Thorac Oncol. 19:252–272. 2024. View Article : Google Scholar : PubMed/NCBI

51 

Drews RM, Hernando B, Tarabichi M, Haase K, Lesluyes T, Smith PS, Morrill Gavarró L, Couturier DL, Liu L, Schneider M, et al: A pan-cancer compendium of chromosomal instability. Nature. 606:976–983. 2022. View Article : Google Scholar : PubMed/NCBI

52 

Chen K, Yang F, Shen H, Wang C, Li X, Chervova O, Wu S, Qiu F, Peng D, Zhu X, et al: Individualized tumor-informed circulating tumor DNA analysis for postoperative monitoring of non-small cell lung cancer. Cancer Cell. 41:1749–1762.e6. 2023. View Article : Google Scholar : PubMed/NCBI

53 

Stejskal P, Goodarzi H, Srovnal J, Hajdúch M, van 't Veer LJ and Magbanua MJM: Circulating tumor nucleic acids: Biology, release mechanisms, and clinical relevance. Mol Cancer. 22:152023. View Article : Google Scholar : PubMed/NCBI

54 

Normanno N, Morabito A, Rachiglio AM, Sforza V, Landi L, Bria E, Delmonte A, Cappuzzo F and De Luca A: Circulating tumour DNA in early stage and locally advanced NSCLC: Ready for clinical implementation? Nat Rev Clin Oncol. 22:215–231. 2025. View Article : Google Scholar : PubMed/NCBI

55 

Black JRM, Karasaki T, Abbott CW, Li B, Veeriah S, Al Bakir M, Liu WK, Huebner A, Martínez-Ruiz C, Pawlik P, et al: Longitudinal ultrasensitive ctDNA monitoring for high-resolution lung cancer risk prediction. Cell. 188:7083–7098.e18. 2025. View Article : Google Scholar : PubMed/NCBI

56 

Schuurbiers MMF, Smith CG, Hartemink KJ, Rintoul RC, Gale D, Monkhorst K, Mandos BLR, Paterson AL, van den Broek D, Rosenfeld N, et al: Recurrence prediction using circulating tumor DNA in patients with early-stage non-small cell lung cancer after treatment with curative intent: A retrospective validation study. PLoS Med. 22:e10045742025. View Article : Google Scholar : PubMed/NCBI

57 

Qiu B, Guo W, Zhang F, Lv F, Ji Y, Peng Y, Chen X, Bao H, Xu Y, Shao Y, et al: Dynamic recurrence risk and adjuvant chemotherapy benefit prediction by ctDNA in resected NSCLC. Nat Commun. 12:67702021. View Article : Google Scholar : PubMed/NCBI

58 

Zhang JT, Liu SY, Gao W, Liu SYM, Yan HH, Ji L, Chen Y, Gong Y, Lu HL, Lin JT, et al: Longitudinal undetectable molecular residual disease defines potentially cured population in localized Non-Small cell lung cancer. Cancer Discov. 12:1690–1701. 2022. View Article : Google Scholar : PubMed/NCBI

59 

Tsui WHA, Jiang P and Lo YMD: Cell-free DNA fragmentomics in cancer. Cancer Cell. 43:1792–1814. 2025. View Article : Google Scholar : PubMed/NCBI

60 

Mathios D, Johansen JS, Cristiano S, Medina JE, Phallen J, Larsen KR, Bruhm DC, Niknafs N, Ferreira L, Adleff V, et al: Detection and characterization of lung cancer using cell-free DNA fragmentomes. Nat Commun. 12:50602021. View Article : Google Scholar : PubMed/NCBI

61 

van 't Erve I, Alipanahi B, Lumbard K, Skidmore ZL, Rinaldi L, Millberg LK, Carey J, Chesnick B, Cristiano S, Portwood C, et al: Cancer treatment monitoring using cell-free DNA fragmentomes. Nat Commun. 15:88012024. View Article : Google Scholar : PubMed/NCBI

62 

Lo YMD, Han DSC, Jiang P and Chiu RWK: Epigenetics, fragmentomics, and topology of cell-free DNA in liquid biopsies. Science. 372:eaaw36162021. View Article : Google Scholar : PubMed/NCBI

63 

Pascual J, Attard G, Bidard FC, Curigliano G, De Mattos-Arruda L, Diehn M, Italiano A, Lindberg J, Merker JD, Montagut C, et al: ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: A report from the ESMO Precision Medicine Working Group. Ann Oncol. 33:750–768. 2022. View Article : Google Scholar : PubMed/NCBI

64 

Abbosh C, Frankell AM, Harrison T, Kisistok J, Garnett A, Johnson L, Veeriah S, Colliver E, Moreau M, Ward S, et al: Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA. Nature. 616:553–562. 2023. View Article : Google Scholar : PubMed/NCBI

65 

Peri A, Salomon N, Wolf Y, Kreiter S, Diken M and Samuels Y: The landscape of T cell antigens for cancer immunotherapy. Nat Cancer. 4:937–954. 2023. View Article : Google Scholar : PubMed/NCBI

66 

Litchfield K, Reading JL, Puttick C, Thakkar K, Abbosh C, Bentham R, Watkins TBK, Rosenthal R, Biswas D, Rowan A, et al: Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition. Cell. 184:596–614.e14. 2021. View Article : Google Scholar : PubMed/NCBI

67 

Memon D, Schoenfeld AJ, Ye D, Fromm G, Rizvi H, Zhang X, Keddar MR, Mathew D, Yoo KJ, Qiu J, et al: Clinical and molecular features of acquired resistance to immunotherapy in non-small cell lung cancer. Cancer Cell. 42:209–224.e9. 2024. View Article : Google Scholar : PubMed/NCBI

68 

Ricciuti B, Arbour KC, Lin JJ, Vajdi A, Vokes N, Hong L, Zhang J, Tolstorukov MY, Li YY, Spurr LF, et al: Diminished efficacy of programmed Death-(Ligand)1 inhibition in STK11- and KEAP1-Mutant lung adenocarcinoma is affected by KRAS mutation status. J Thorac Oncol. 17:399–410. 2022. View Article : Google Scholar : PubMed/NCBI

69 

Ricciuti B and Garassino MC: Precision immunotherapy for STK11/KEAP1-mutant NSCLC. J Thorac Oncol. 19:877–882. 2024. View Article : Google Scholar : PubMed/NCBI

70 

Huang Y, Lu C, Wang H, Gu L, Fu YX and Li GM: DNAJA2 deficiency activates cGAS-STING pathway via the induction of aberrant mitosis and chromosome instability. Nat Commun. 14:52462023. View Article : Google Scholar : PubMed/NCBI

71 

Li J, Hubisz MJ, Earlie EM, Duran MA, Hong C, Varela AA, Tsao JL, Petersson EJ, Lok BH, Modrek AS, et al: Non-cell-autonomous cancer progression from chromosomal instability. Nature. 620:1080–1088. 2023. View Article : Google Scholar : PubMed/NCBI

72 

Heymach JV, Harpole D, Mitsudomi T, Taube JM, Galffy G, Hochmair M, Winder T, Zukov R, Garbaos G, Gao S, et al: Perioperative durvalumab for resectable Non-Small-Cell lung cancer. N Engl J Med. 389:1672–1684. 2023. View Article : Google Scholar : PubMed/NCBI

73 

Cascone T, Awad MM, Spicer JD, He J, Lu S, Sepesi B, Tanaka F, Taube JM, Cornelissen R, Havel L, et al: Perioperative nivolumab in resectable lung cancer. N Engl J Med. 390:1756–1769. 2024. View Article : Google Scholar : PubMed/NCBI

74 

Sorin M, Prosty C, Ghaleb L, Nie K, Katergi K, Shahzad MH, Dubé LR, Atallah A, Swaby A, Dankner M, et al: Neoadjuvant Chemoimmunotherapy for NSCLC: A systematic review and meta-analysis. JAMA Oncol. 10:621–633. 2024. View Article : Google Scholar : PubMed/NCBI

75 

Vaccaro A, Rahal Z, Kadara H and Cascone T: A roadmap to precision immunotherapy for Early-stage non-small cell lung cancer. Cancer Discov. 15:884–889. 2025. View Article : Google Scholar : PubMed/NCBI

76 

Xia L, Mei J, Kang R, Deng S, Chen Y, Yang Y, Feng G, Deng Y, Gan F, Lin Y, et al: Perioperative ctDNA-Based molecular residual disease detection for Non-Small cell lung cancer: A prospective multicenter cohort study (LUNGCA-1). Clin Cancer Res. 28:3308–3317. 2022. View Article : Google Scholar : PubMed/NCBI

77 

Zer A, Ahn MJ, Barlesi F, Bubendorf L, De Ruysscher D, Garrido P, Gautschi O, Hendriks LE, Jänne PA, Kerr KM, et al: Early and locally advanced non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 36:1245–1262. 2025. View Article : Google Scholar : PubMed/NCBI

78 

Drew Y, Zenke FT and Curtin NJ: DNA damage response inhibitors in cancer therapy: Lessons from the past, current status and future implications. Nat Rev Drug Discov. 24:19–39. 2025. View Article : Google Scholar : PubMed/NCBI

79 

Tsilingiri K, Chalari A, Christopoulou G, Voutsina A, Constantoulakis P, Potaris K, Vamvakaris I, Hatzidaki D, Zachou G, Vatsellas G, et al: Genomic scarring score predicts the response to PARP inhibitors in non-small cell lung cancer. NPJ Precis Oncol. 8:2912024. View Article : Google Scholar : PubMed/NCBI

80 

Yap TA, Fontana E, Lee EK, Spigel DR, Højgaard M, Lheureux S, Mettu NB, Carneiro BA, Carter L, Plummer R, et al: Camonsertib in DNA damage response-deficient advanced solid tumors: Phase 1 trial results. Nat Med. 29:1400–1411. 2023. View Article : Google Scholar : PubMed/NCBI

81 

Yap TA, Tan DSP, Terbuch A, Caldwell R, Guo C, Goh BC, Heong V, Noor NR, Bashir S, Drew Y, et al: First-in-Human trial of the oral ataxia telangiectasia and RAD3-Related (ATR) inhibitor BAY 1895344 in patients with advanced solid tumors. Cancer Discov. 11:80–91. 2021. View Article : Google Scholar : PubMed/NCBI

82 

Fukuda K, Takeuchi S, Arai S, Nanjo S, Sato S, Kotani H, Kita K, Nishiyama A, Sakaguchi H, Ohtsubo K, et al: Targeting WEE1 enhances the antitumor effect of KRAS-mutated non-small cell lung cancer harboring TP53 mutations. Cell Rep Med. 5:1015782024. View Article : Google Scholar : PubMed/NCBI

83 

Yap TA, LoRusso P, Miller RE, Kristeleit R, Paulovich AG, McMorn S, Oplustil O'Connor L, Lombardi B, Marco-Casanova P, Gangl ET, et al: The DNA-PK inhibitor AZD7648 alone or combined with pegylated liposomal doxorubicin in patients with advanced cancer: Results of a first-in-human Phase I/IIa study. Br J Cancer. 133:168–177. 2025. View Article : Google Scholar : PubMed/NCBI

84 

da Costa AABA, Chowdhury D, Shapiro GI, D'Andrea AD and Konstantinopoulos PA: Targeting replication stress in cancer therapy. Nat Rev Drug Discov. 22:38–58. 2023. View Article : Google Scholar : PubMed/NCBI

85 

Besse B, Pons-Tostivint E, Park K, Hartl S, Forde PM, Hochmair MJ, Awad MM, Thomas M, Goss G, Wheatley-Price P, et al: Biomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: A phase 2 umbrella trial. Nat Med. 30:716–729. 2024. View Article : Google Scholar : PubMed/NCBI

86 

Gray JE, Schenker M, Şendur MAN, Leonova V, Kowalski D, Kato T, Orlova R, Yang JC, Langleben A, Pilz A, et al: The Phase 3 KEYLYNK-006 study of pembrolizumab plus olaparib versus pembrolizumab plus pemetrexed as maintenance therapy for metastatic nonsquamous NSCLC. J Thorac Oncol. 20:219–232. 2025. View Article : Google Scholar : PubMed/NCBI

87 

Hochmair M, Schenker M, Cobo Dols M, Kim TM, Ozyilkan O, Smagina M, Leonova V, Kato T, Fedenko A, De Angelis F, et al: Pembrolizumab with or without maintenance olaparib for metastatic squamous NSCLC that responded to First-Line pembrolizumab plus chemotherapy. J Thorac Oncol. 20:203–218. 2025. View Article : Google Scholar : PubMed/NCBI

88 

Cleary JM, Aguirre AJ, Shapiro GI and D'Andrea AD: Biomarker-guided development of DNA repair inhibitors. Mol Cell. 78:1070–1085. 2020. View Article : Google Scholar : PubMed/NCBI

89 

Bailey C, Pich O, Thol K, Watkins TBK, Luebeck J, Rowan A, Stavrou G, Weiser NE, Dameracharla B, Bentham R, et al: Origins and impact of extrachromosomal DNA. Nature. 635:193–200. 2024. View Article : Google Scholar : PubMed/NCBI

90 

Hung KL, Yost KE, Xie L, Shi Q, Helmsauer K, Luebeck J, Schöpflin R, Lange JT, Chamorro González R, Weiser NE, et al: ecDNA hubs drive cooperative intermolecular oncogene expression. Nature. 600:731–736. 2021. View Article : Google Scholar : PubMed/NCBI

91 

Rami-Porta R, Nishimura KK, Giroux DJ, Detterbeck FC, Asamura H, Goldstraw P, Crowley J, Chansky K, Edwards J, Nicholson AG, et al: The international association for the study of lung cancer lung cancer staging project: Proposals for revision of the TNM stage groups in the forthcoming (Ninth) edition of the TNM classification for lung cancer. J Thorac Oncol. 19:1007–1027. 2024. View Article : Google Scholar : PubMed/NCBI

92 

Spicer JD, Cascone T, Wynes MW, Ahn MJ, Dacic S, Felip E, Forde PM, Higgins KA, Kris MG, Mitsudomi T, et al: Neoadjuvant and adjuvant treatments for early stage resectable NSCLC: Consensus recommendations from the international association for the study of lung cancer. J Thorac Oncol. 19:1373–1414. 2024. View Article : Google Scholar : PubMed/NCBI

93 

Wu YL, Dziadziuszko R, Ahn JS, Barlesi F, Nishio M, Lee DH, Lee JS, Zhong W, Horinouchi H, Mao W, et al: Alectinib in resected ALK-Positive Non-Small-Cell lung cancer. N Engl J Med. 390:1265–1276. 2024. View Article : Google Scholar : PubMed/NCBI

94 

Passaro A, Al Bakir M, Hamilton EG, Diehn M, André F, Roy-Chowdhuri S, Mountzios G, Wistuba II, Swanton C and Peters S: Cancer biomarkers: Emerging trends and clinical implications for personalized treatment. Cell. 187:1617–1635. 2024. View Article : Google Scholar : PubMed/NCBI

95 

Steele CD, Abbasi A, Islam SMA, Bowes AL, Khandekar A, Haase K, Hames-Fathi S, Ajayi D, Verfaillie A, Dhami P, et al: Signatures of copy number alterations in human cancer. Nature. 606:984–991. 2022. View Article : Google Scholar : PubMed/NCBI

96 

Biswas D, Liu YH, Herrero J, Wu Y, Moore DA, Karasaki T, Grigoriadis K, Lu WT, Veeriah S, Naceur-Lombardelli C, et al: Prospective validation of ORACLE, a clonal expression biomarker associated with survival of patients with lung adenocarcinoma. Nat Cancer. 6:86–101. 2025. View Article : Google Scholar : PubMed/NCBI

97 

Groelly FJ, Fawkes M, Dagg RA, Blackford AN and Tarsounas M: Targeting DNA damage response pathways in cancer. Nat Rev Cancer. 23:78–94. 2023. View Article : Google Scholar : PubMed/NCBI

98 

Wong IT, Yi H, Melillo B, Cravatt BF, Chang HY and Mischel PS: Targeting extrachromosomal DNA in human cancers. Nat Rev Drug Discov. 25:374–389. 2026. View Article : Google Scholar : PubMed/NCBI

99 

Al-Rawi DH, Lettera E, Li J, DiBona M and Bakhoum SF: Targeting chromosomal instability in patients with cancer. Nat Rev Clin Oncol. 21:645–659. 2024. View Article : Google Scholar : PubMed/NCBI

100 

Tan AC, Liao BC, Li M, Lee D, Uehara Y, Thamlikitkul L, Zhang JT, Zheng M, Lee CK, Pavlakis N, et al: Consensus statement on ctDNA minimal residual disease testing in early stage NSCLC: A Delphi study by the Asian thoracic oncology research group. J Thorac Oncol. 21:1036962026. View Article : Google Scholar : PubMed/NCBI

101 

Karasaki T, Moore DA, Veeriah S, Naceur-Lombardelli C, Toncheva A, Magno N, Ward S, Bakir MA, Watkins TBK, Grigoriadis K, et al: Evolutionary characterization of lung adenocarcinoma morphology in TRACERx. Nat Med. 29:833–845. 2023. View Article : Google Scholar : PubMed/NCBI

102 

Malki Y, Zhou Q, Jiang P and Lo YMD: The comings and goings of cell-free DNA: Biological and clinical implications. Med. 7:1009262026. View Article : Google Scholar : PubMed/NCBI

103 

Hayes DF: Defining clinical utility of tumor biomarker tests: A Clinician's Viewpoint. J Clin Oncol. 39:238–248. 2021. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wang L, Feng Y and Liu Q: Genomic instability, postoperative recurrence and therapeutic vulnerabilities in resectable non‑small cell lung cancer (Review). Oncol Rep 56: 182, 2026.
APA
Wang, L., Feng, Y., & Liu, Q. (2026). Genomic instability, postoperative recurrence and therapeutic vulnerabilities in resectable non‑small cell lung cancer (Review). Oncology Reports, 56, 182. https://doi.org/10.3892/or.2026.9188
MLA
Wang, L., Feng, Y., Liu, Q."Genomic instability, postoperative recurrence and therapeutic vulnerabilities in resectable non‑small cell lung cancer (Review)". Oncology Reports 56.4 (2026): 182.
Chicago
Wang, L., Feng, Y., Liu, Q."Genomic instability, postoperative recurrence and therapeutic vulnerabilities in resectable non‑small cell lung cancer (Review)". Oncology Reports 56, no. 4 (2026): 182. https://doi.org/10.3892/or.2026.9188
Copy and paste a formatted citation
x
Spandidos Publications style
Wang L, Feng Y and Liu Q: Genomic instability, postoperative recurrence and therapeutic vulnerabilities in resectable non‑small cell lung cancer (Review). Oncol Rep 56: 182, 2026.
APA
Wang, L., Feng, Y., & Liu, Q. (2026). Genomic instability, postoperative recurrence and therapeutic vulnerabilities in resectable non‑small cell lung cancer (Review). Oncology Reports, 56, 182. https://doi.org/10.3892/or.2026.9188
MLA
Wang, L., Feng, Y., Liu, Q."Genomic instability, postoperative recurrence and therapeutic vulnerabilities in resectable non‑small cell lung cancer (Review)". Oncology Reports 56.4 (2026): 182.
Chicago
Wang, L., Feng, Y., Liu, Q."Genomic instability, postoperative recurrence and therapeutic vulnerabilities in resectable non‑small cell lung cancer (Review)". Oncology Reports 56, no. 4 (2026): 182. https://doi.org/10.3892/or.2026.9188
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team