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Cited by 197Lung Cancer Treatments and MutationsLung Cancer Research StudiesLung Cancer Diagnosis and Treatment

Advances in molecular pathology and therapy of non-small cell lung cancer

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Huang, Qing, Li, Yuanxiang, Huang, Yingdan, Wu, Jingyi, Bao, Wendai, Xue, Chang, Li, Xiaoyu, Dong, Shuang +2 more·2025·Signal Transduction and Targeted Therapy
DOI 10.1038/s41392-025-02243-6PMC PMC12167388
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Abstract

Over the past two decades, non-small cell lung cancer (NSCLC) has witnessed encouraging advancements in basic and clinical research. However, substantial unmet needs remain for patients worldwide, as drug resistance persists as an inevitable reality. Meanwhile, the journey towards amplifying the breadth and depth of the therapeutic effect requires comprehending and integrating diverse and profound progress. In this review, therefore, we aim to comprehensively present such progress that spans the various aspects of molecular pathology, encompassing elucidations of metastatic mechanisms, identification of therapeutic targets, and dissection of spatial omics. Additionally, we also highlight the numerous small molecule and antibody drugs, encompassing their application alone or in combination, across later-line, frontline, neoadjuvant or adjuvant settings. Then, we elaborate on drug resistance mechanisms, mainly involving targeted therapies and immunotherapies, revealed by our proposed theoretical models to clarify interactions between cancer cells and a variety of non-malignant cells, as well as almost all the biological regulatory pathways. Finally, we outline mechanistic perspectives to pursue innovative treatments of NSCLC, through leveraging artificial intelligence to incorporate the latest insights into the design of finely-tuned, biomarker-driven combination strategies. This review not only provides an overview of the various strategies of how to reshape available armamentarium, but also illustrates an example of clinical translation of how to develop novel targeted drugs, to revolutionize therapeutic landscape for NSCLC.

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  1. [1]Spiro, S. G. & Silvestri, G. A. One hundred years of lung cancer. Am. J. Respir. Crit. Care Med. 172, 523–529 (2005). 15961694 · DOI
  2. [4]Baker, T. M., Waise, S., Tarabichi, M. & Van Loo, P. Aneuploidy and complex genomic rearrangements in cancer evolution. Nat. Cancer 5, 228–239 (2024). 38286829 PMC7616040 · DOI
  3. [5]Soerjomataram, I. & Bray, F. Planning for tomorrow: global cancer incidence and the role of prevention 2020-2070. Nat. Rev. Clin. Oncol. 18, 663–672 (2021). 34079102 · DOI · Paper page
  4. [6]Swanton, C. et al. Embracing cancer complexity: Hallmarks of systemic disease. Cell 187, 1589–1616 (2024). 38552609 PMC12077170 · DOI
  5. [7]Brewer, L. A. 3rd Historical notes on lung cancer before and after Graham’s successful pneumonectomy in 1933. Am. J. Surg. 143, 650–659 (1982). 7046483 · DOI
  6. [8]Cullen, M. Lung cancer. 4: chemotherapy for non-small cell lung cancer: the end of the beginning. Thorax 58, 352–356 (2003). 12668803 PMC1746634 · DOI
  7. [9]Doll, R. & Hill, A. B. Smoking and carcinoma of the lung; preliminary report. Br. Med. J. 2, 739–748 (1950). 14772469 PMC2038856 · DOI · Paper page
  8. [10]Stevens, W. E. Radiation therapy in lung cancer. Geriatrics 20, 816–834 (1965). 5319415
  9. [11]Clement-Duchene, C. et al. [Protocols for lung cancer screening: Limitations, and consequences]. Rev. Mal. Respir. 27, 314–328 (2010). 20403542
  10. [12]Non-small Cell Lung Cancer Collaborative, G Chemotherapy for non-small cell lung cancer. Cochrane Database Syst. Rev. 2000, CD002139 (2000). 10796867 PMC10627435
  11. [13]Calvo, A. R. & Belani, C. P. Lung cancer: therapeutic options for stage IV and recurrent NSCLC. Cancer Treat. Res. 105, 189–227 (2001). 11224988 · DOI
  12. [14]Singh, S., Sadhukhan, S. & Sonawane, A. 20 years since the approval of first EGFR-TKI, gefitinib: Insight and foresight. Biochim. Biophys. Acta Rev. Cancer 1878, 188967 (2023). 37657684 · DOI
  13. [15]Clement-Duchene, C., Godbert, B. & Martinet, Y. Anti-angiogenic agents in the treatment of lung cancer: indications and toxicities]. Rev. Mal. Respir. 29, 161–177 (2012). 22405111
  14. [16]Desai, A. & Peters, S. Immunotherapy-based combinations in metastatic NSCLC. Cancer Treat. Rev. 116, 102545 (2023). 37030062 · DOI
  15. [17]Wang, M., Herbst, R. S. & Boshoff, C. Toward personalized treatment approaches for non-small-cell lung cancer. Nat. Med. 27, 1345–1356 (2021). 34385702 · DOI
  16. [19]LoPiccolo, J., Gusev, A., Christiani, D. C. & Janne, P. A. Lung cancer in patients who have never smoked - an emerging disease. Nat. Rev. Clin. Oncol. 21, 121–146 (2024). 38195910 PMC11014425 · DOI
  17. [21]Srivastava, S. et al. Cancer overdiagnosis: a biological challenge and clinical dilemma. Nat. Rev. Cancer 19, 349–358 (2019). 31024081 PMC8819710 · DOI
  18. [22]Benzaquen, J. et al. Integrating artificial intelligence into lung cancer screening: a randomised controlled trial protocol. BMJ Open 14, e074680 (2024). 38355174 PMC10868245 · DOI
  19. [23]Laguna, J. C. et al. Geographic differences in lung cancer: focus on carcinogens, genetic predisposition, and molecular epidemiology. Ther. Adv. Med. Oncol. 16, 17588359241231260 (2024). PMC10919138 38455708
  20. [24]Hong, L. et al. Molecular landscape of ERBB2 alterations in 3000 advanced NSCLC patients. NPJ Precis Oncol. 8, 217 (2024). 39354054 PMC11445497 · DOI
  21. [25]Padinharayil, H. et al. Non-small cell lung carcinoma (NSCLC): Implications on molecular pathology and advances in early diagnostics and therapeutics. Genes Dis. 10, 960–989 (2023). 37396553 PMC10308181 · DOI
  22. [26]Sanchez-Danes, A. & Blanpain, C. Deciphering the cells of origin of squamous cell carcinomas. Nat. Rev. Cancer 18, 549–561 (2018). 29849070 PMC7170720 · DOI
  23. [27]Lau, S. C. M., Pan, Y., Velcheti, V. & Wong, K. K. Squamous cell lung cancer: Current landscape and future therapeutic options. Cancer Cell 40, 1279–1293 (2022). 36270277 · DOI
  24. [28]Moreira, A. L. et al. A Grading System for Invasive Pulmonary Adenocarcinoma: A Proposal From the International Association for the Study of Lung Cancer Pathology Committee. J. Thorac. Oncol. 15, 1599–1610 (2020). 32562873 PMC8362286 · DOI
  25. [29]Callister, M. E. J. & de Koning, H. J. Lung cancer screening in never-smokers: a balancing act. Lancet Respir. Med. 12, 93–94 (2024). 38042166 · DOI
  26. [30]Burr, R. et al. Developmental mosaicism underlying EGFR-mutant lung cancer presenting with multiple primary tumors. Nat Cancer5, 1681–1696 (2024). PMC11584400 39406916
  27. [31]Gridelli, C. et al. Non-small-cell lung cancer. Nat. Rev. Dis. Prim. 1, 15009 (2015). 27188576 · DOI
  28. [32]Herbst, R. S., Morgensztern, D. & Boshoff, C. The biology and management of non-small cell lung cancer. Nature 553, 446–454 (2018). 29364287 · DOI · Paper page
  29. [33]Yatabe, Y. Molecular pathology of non-small cell carcinoma. Histopathology 84, 50–66 (2024). 37936491 · DOI
  30. [34]Rosell, R. et al. Screening for epidermal growth factor receptor mutations in lung cancer. N. Engl. J. Med. 361, 958–967 (2009). 19692684 · DOI · Paper page
  31. [35]Shi, Y. et al. A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). J. Thorac. Oncol. 9, 154–162 (2014). 24419411 PMC4132036 · DOI
  32. [36]Sands, J. M. et al. Next-generation sequencing informs diagnosis and identifies unexpected therapeutic targets in lung squamous cell carcinomas. Lung Cancer 140, 35–41 (2020). 31855703 · DOI
  33. [37]Lam, V. K. et al. Targeted Tissue and Cell-Free Tumor DNA Sequencing of Advanced Lung Squamous-Cell Carcinoma Reveals Clinically Significant Prevalence of Actionable Alterations. Clin. Lung Cancer 20, 30–36.e33 (2019). 30279110 · DOI
  34. [39]Friedlaender, A. et al. EGFR and HER2 exon 20 insertions in solid tumours: from biology to treatment. Nat. Rev. Clin. Oncol. 19, 51–69 (2022). 34561632 · DOI
  35. [40]Onitsuka, T. et al. Acquired resistance to gefitinib: the contribution of mechanisms other than the T790M, MET, and HGF status. Lung Cancer 68, 198–203 (2010). 19589612 · DOI
  36. [41]Tung, N. et al. Selection of Germline Genetic Testing Panels in Patients With Cancer: ASCO Guideline. J. Clin. Oncol. 42, 2599–2615 (2024). 38759122 · DOI
  37. [42]Lim, T. K. H. et al. In advanced NSCLC: Prevalence, co-mutations, and testing. Lung Cancer. 184, 107293 (2023). 37683526
  38. [43]Vassella, E. et al. Mutational profiles of primary pulmonary adenocarcinoma and paired brain metastases disclose the importance of KRAS mutations. Eur. J. Cancer 159, 227–236 (2021). 34781171 · DOI
  39. [44]Molina-Arcas, M. & Downward, J. Exploiting the therapeutic implications of KRAS inhibition on tumor immunity. Cancer Cell 42, 338–357 (2024). 38471457 · DOI · Paper page
  40. [45]Kim, J. O. et al. KIF5B-RET Fusion gene may coincide oncogenic mutations of EGFR or KRAS gene in lung adenocarcinomas. Diagn. Pathol. 10, 143 (2015). 26268359 PMC4535765 · DOI
  41. [46]Fukuda, A. & Yoshida, T. Treatment of advanced ALK-rearranged NSCLC following second-generation ALK-TKI failure. Expert Rev. Anticancer Ther. 23, 1157–1167 (2023). 37772744 · DOI
  42. [47]Shaw, A. T. & Engelman, J. A. ALK in lung cancer: past, present, and future. J. Clin. Oncol. 31, 1105–1111 (2013). 23401436 PMC4209068 · DOI
  43. [48]Soda, M. et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 448, 561–566 (2007). 17625570 · DOI · Paper page
  44. [49]Drilon, A. et al. ROS1-dependent cancers - biology, diagnostics and therapeutics. Nat. Rev. Clin. Oncol. 18, 35–55 (2021). 32760015 PMC8830365 · DOI
  45. [50]Shaw, A. T. et al. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N. Engl. J. Med. 371, 1963–1971 (2014). 25264305 PMC4264527 · DOI · Paper page
  46. [51]Roviello, G. et al. Advances in anti-BRAF therapies for lung cancer. Invest N. Drugs 39, 879–890 (2021). PMC8068629 33474634 · DOI
  47. [52]Facchinetti, F. et al. Molecular mechanisms of resistance to BRAF and MEK inhibitors in BRAF(V600E) non-small cell lung cancer. Eur. J. Cancer 132, 211–223 (2020). 32388065 · DOI
  48. [53]Cocco, E., Scaltriti, M. & Drilon, A. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat. Rev. Clin. Oncol. 15, 731–747 (2018). 30333516 PMC6419506 · DOI
  49. [54]Repetto, M. et al. NTRK gene fusion testing and management in lung cancer. Cancer Treat. Rev. 127, 102733 (2024). 38733648 · DOI
  50. [55]Hempel, D. et al. Antitumor Activity of Larotrectinib in Esophageal Carcinoma with NTRK Gene Amplification. Oncologist 25, e881–e886 (2020). 32323889 PMC7288663 · DOI
  51. [56]Pecci, F. et al. Activating Point Mutations in the MET Kinase Domain Represent a Unique Molecular Subset of Lung Cancer and Other Malignancies Targetable with MET Inhibitors. Cancer Discov. 14, 1440–1456 (2024). 38564707 PMC11294820 · DOI
  52. [57]Wolf, J. et al. Capmatinib in MET Exon 14-Mutated or MET-Amplified Non-Small-Cell Lung Cancer. N. Engl. J. Med. 383, 944–957 (2020). 32877583 · DOI
  53. [58]Awad, M. M. et al. MET Exon 14 Mutations in Non-Small-Cell Lung Cancer Are Associated With Advanced Age and Stage-Dependent MET Genomic Amplification and c-Met Overexpression. J. Clin. Oncol. 34, 721–730 (2016). 26729443 · DOI
  54. [59]Le, X. et al. Landscape and Clonal Dominance of Co-occurring Genomic Alterations in Non-Small-Cell Lung Cancer Harboring MET Exon 14 Skipping. JCO Precis Oncol. 5, (2021). PMC8694524 34957368
  55. [60]Servetto, A. et al. RET rearrangements in non-small cell lung cancer: Evolving treatment landscape and future challenges. Biochim. Biophys. Acta Rev. Cancer 1877, 188810 (2022). 36202311 · DOI
  56. [61]Kato, S. et al. RET Aberrations in Diverse Cancers: Next-Generation Sequencing of 4,871 Patients. Clin. Cancer Res. 23, 1988–1997 (2017). 27683183 · DOI
  57. [63]Pillai, R. N. et al. HER2 mutations in lung adenocarcinomas: A report from the Lung Cancer Mutation Consortium. Cancer 123, 4099–4105 (2017). 28743157 PMC5650517 · DOI
  58. [64]Wang, C. et al. Analyses of rare predisposing variants of lung cancer in 6,004 whole genomes in Chinese. Cancer Cell 40, 1223–1239.e1226 (2022). 36113475 · DOI
  59. [65]Karasaki, T. et al. Evolutionary characterization of lung adenocarcinoma morphology in TRACERx. Nat. Med. 29, 833–845 (2023). 37045996 PMC7614478 · DOI
  60. [66]Mattei, A. L., Bailly, N. & Meissner, A. DNA methylation: a historical perspective. Trends Genet 38, 676–707 (2022). 35504755 · DOI
  61. [67]Zhang, R. et al. EGLN2 DNA methylation and expression interact with HIF1A to affect survival of early-stage NSCLC. Epigenetics 14, 118–129 (2019). 30665327 PMC6557590 · DOI
  62. [68]Strahl, B. D. & Allis, C. D. The language of covalent histone modifications. Nature 403, 41–45 (2000). 10638745 · DOI · Paper page
  63. [69]Eichner, L. J. et al. HDAC3 is critical in tumor development and therapeutic resistance in Kras-mutant non-small cell lung cancer. Sci. Adv. 9, eadd3243 (2023). 36930718 PMC10022903 · DOI
  64. [70]Zhao, K. et al. MOF-mediated acetylation of SIRT6 disrupts SIRT6-FOXA2 interaction and represses SIRT6 tumor-suppressive function by upregulating ZEB2 in NSCLC. Cell Rep. 42, 112939 (2023). 37566546 · DOI
  65. [71]Takashina, T. et al. Combined inhibition of EZH2 and histone deacetylases as a potential epigenetic therapy for non-small-cell lung cancer cells. Cancer Sci. 107, 955–962 (2016). 27116120 PMC4946723 · DOI
  66. [72]Li, J. et al. The molecular landscape of histone lysine methyltransferases and demethylases in non-small cell lung cancer. Int. J. Med. Sci. 16, 922–930 (2019). 31341405 PMC6643118 · DOI
  67. [73]Sasa, G. B. K. et al. Clinicopathological implications of lncRNAs, immunotherapy and DNA methylation in lung squamous cell carcinoma: a narrative review. Transl. Cancer Res. 10, 5406–5429 (2021). 35116387 PMC8799054 · DOI
  68. [74]Liang, G. et al. miR-196b-5p-mediated downregulation of TSPAN12 and GATA6 promotes tumor progression in non-small cell lung cancer. Proc. Natl. Acad. Sci. USA 117, 4347–4357 (2020). 32041891 PMC7049122 · DOI
  69. [75]Chen, Y., Zhou, X., Qiao, J. & Bao, A. MiR-142-3p Overexpression Increases Chemo-Sensitivity of NSCLC by Inhibiting HMGB1-Mediated Autophagy. Cell Physiol. Biochem. 41, 1370–1382 (2017). 28427045 · DOI
  70. [76]Li, B. et al. circNDUFB2 inhibits non-small cell lung cancer progression via destabilizing IGF2BPs and activating anti-tumor immunity. Nat. Commun. 12, 295 (2021). 33436560 PMC7804955 · DOI · Paper page
  71. [77]Chen, J. et al. LINC00173.v1 promotes angiogenesis and progression of lung squamous cell carcinoma by sponging miR-511-5p to regulate VEGFA expression. Mol. Cancer 19, 98 (2020). 32473645 PMC7260858 · DOI
  72. [78]Esteller, M. et al. The Epigenetic Hallmarks of Cancer. Cancer Discov. 14, 1783–1809 (2024). 39363741 · DOI
  73. [80]Martínez-Ruiz, C. et al. Genomic-transcriptomic evolution in lung cancer and metastasis. Nature 616, 543 (2023). 37046093 PMC10115639 · DOI
  74. [81]Hynds, R. E. et al. Representation of genomic intratumor heterogeneity in multi-region non-small cell lung cancer patient-derived xenograft models. Nat. Commun. 15, 4653 (2024). 38821942 PMC11143323 · DOI
  75. [82]Jamal-Hanjani, M. et al. Tracking the Evolution of Non-Small-Cell Lung Cancer. N. Engl. J. Med. 376, 2109–2121 (2017). 28445112 · DOI · Paper page
  76. [83]Han, G. et al. An atlas of epithelial cell states and plasticity in lung adenocarcinoma. Nature 627, 656–663 (2024). 38418883 PMC10954546 · DOI
  77. [84]Wu, F. et al. Single-cell profiling of tumor heterogeneity and the microenvironment in advanced non-small cell lung cancer. Nat. Commun. 12, 2540 (2021). 33953163 PMC8100173 · DOI
  78. [85]Tirosh, I. & Suva, M. L. Cancer cell states: Lessons from ten years of single-cell RNA-sequencing of human tumors. Cancer Cell 42, 1497–1506 (2024). 39214095 · DOI
  79. [86]Xie, S. M. et al. The metastasizing mechanisms of lung cancer: Recent advances and therapeutic challenges. Biomed. Pharmacotherapy. 138, 111450 (2021). 33690088
  80. [87]Rabas, N., Ferreira, R. M. M., Di Blasio, S. & Malanchi, I. Cancer-induced systemic pre-conditioning of distant organs: building a niche for metastatic cells. Nat. Rev. Cancer 24, 829–849 (2024). 39390247 · DOI
  81. [88]Steeg, P. S. Tumor metastasis: mechanistic insights and clinical challenges. Nat. Med. 12, 895–904 (2006). 16892035 · DOI
  82. [89]Fares, J. et al. Molecular principles of metastasis: a hallmark of cancer revisited. Sig. Transduct. Target Ther. 5, 28 (2020). PMC7067809 32296047 · DOI
  83. [91]Yarden, Y. & Sliwkowski, M. X. Untangling the ErbB signalling network. Nat. Rev. Mol. Cell Biol. 2, 127–137 (2001). 11252954 · DOI · Paper page
  84. [92]Nilsson, M. B. et al. Altered Regulation of HIF-1alpha in Naive- and Drug-Resistant EGFR-Mutant NSCLC: Implications for a Vascular Endothelial Growth Factor-Dependent Phenotype. J. Thorac. Oncol. 16, 439–451 (2021). 33309987 PMC8207565 · DOI
  85. [93]Park, S. M., Gaur, A. B., Lengyel, E. & Peter, M. E. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 22, 894–907 (2008). 18381893 PMC2279201 · DOI · Paper page
  86. [94]Zhao, Z., Zhang, L., Yao, Q. & Tao, Z. miR-15b regulates cisplatin resistance and metastasis by targeting PEBP4 in human lung adenocarcinoma cells. Cancer Gene Ther. 22, 108–114 (2015). 25721211 · DOI
  87. [95]Cords, L. et al. Cancer-associated fibroblast phenotypes are associated with patient outcome in non-small cell lung cancer. Cancer Cell. 42, 396–412.e5 (2024). PMC10929690 38242124
  88. [96]Wu, F. et al. Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer. Sig. Transduct. Target Ther. 6, 218 (2021). PMC8190181 34108441 · DOI · Paper page
  89. [97]Wong, K. Y. et al. Cancer-associated fibroblasts in nonsmall cell lung cancer: From molecular mechanisms to clinical implications. Int. J. Cancer 151, 1195–1215 (2022). 35603909 PMC9545594 · DOI
  90. [98]Linke, J. A., Munn, L. L. & Jain, R. K. Compressive stresses in cancer: characterization and implications for tumour progression and treatment. Nat. Rev. Cancer 24, 768–791 (2024). 39390249 PMC12967324 · DOI
  91. [99]Merchant, N. et al. Matrix metalloproteinases: their functional role in lung cancer. Carcinogenesis 38, 766–780 (2017). 28637319 · DOI
  92. [100]Gocheva, V. et al. Quantitative proteomics identify Tenascin-C as a promoter of lung cancer progression and contributor to a signature prognostic of patient survival. Proc. Natl. Acad. Sci. USA 114, E5625–E5634 (2017). 28652369 PMC5514763 · DOI
  93. [101]Gueguen, P. et al. Contribution of resident and circulating precursors to tumor-infiltrating CD8(+) T cell populations in lung cancer. Sci Immunol. 6, 396–412.e5 (2021). 33514641
  94. [102]Haynes, N. M., Chadwick, T. B. & Parker, B. S. The complexity of immune evasion mechanisms throughout the metastatic cascade. Nat. Immunol. 25, 1793–1808 (2024). 39285252 · DOI
  95. [103]Coelho, A. L. et al. Angiogenesis in NSCLC: is vessel co-option the trunk that sustains the branches?. Oncotarget 8, 39795–39804 (2017). 26950275 PMC5503654 · DOI
  96. [104]Bauman, J. E., Eaton, K. D. & Martins, R. G. Antagonism of platelet-derived growth factor receptor in non small cell lung cancer: rationale and investigations. Clin. Cancer Res. 13, s4632–s4636 (2007). 17671155 · DOI
  97. [105]Sivanand, S. et al. Cancer tissue of origin constrains the growth and metabolism of metastases. Nat. Metab. 6, 1668–1681 (2024). 39160333 PMC11450831 · DOI
  98. [106]Tagore, S. et al. Single-cell and spatial genomic landscape of non-small cell lung cancer brain metastases. Nat. Med. 31, 1351–1363 (2025). 40016452 PMC12323702 · DOI
  99. [107]Schenkel, J. M. & Pauken, K. E. Localization, tissue biology and T cell state - implications for cancer immunotherapy. Nat. Rev. Immunol. 23, 807–823 (2023). 37253877 PMC11448857 · DOI
  100. [108]Goodwin, R. J. A., Platz, S. J., Reis-Filho, J. S. & Barry, S. T. Accelerating Drug Development Using Spatial Multi-omics. Cancer Discov. 14, 620–624 (2024). 38571424 · DOI
  101. [109]Thol, K., Pawlik, P. & McGranahan, N. Therapy sculpts the complex interplay between cancer and the immune system during tumour evolution. Genome Med. 14, 137 (2022). 36476325 PMC9730559 · DOI
  102. [110]Kim, J. et al. Spatial profiling of non-small cell lung cancer provides insights into tumorigenesis and immunotherapy response. Commun. Biol. 7, 930 (2024). 39095464 PMC11297140 · DOI
  103. [111]Takei, Y. et al. Integrated spatial genomics reveals global architecture of single nuclei. Nature 590, 344–350 (2021). 33505024 PMC7878433 · DOI
  104. [113]Skoulidis, F. et al. CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors. Nature 635, 462–471 (2024). 39385035 PMC11560846 · DOI · Paper page
  105. [115]Janssens, D. H. et al. Automated CUT&Tag profiling of chromatin heterogeneity in mixed-lineage leukemia. Nat. Genet. 53, 1586–1596 (2021). 34663924 PMC8571097 · DOI
  106. [116]Elhanani, O., Ben-Uri, R. & Keren, L. Spatial profiling technologies illuminate the tumor microenvironment. Cancer Cell 41, 404–420 (2023). 36800999 · DOI
  107. [117]Mo, C. K. et al. Tumour evolution and microenvironment interactions in 2D and 3D space. Nature 634, 1178–1186 (2024). 39478210 PMC11525187 · DOI
  108. [118]Walker, C. & Angelo, M. Toward clinical applications of spatial-omics in cancer research. Nat. Cancer 5, 1771–1773 (2024). 39690225 · DOI
  109. [119]Black, S. et al. CODEX multiplexed tissue imaging with DNA-conjugated antibodies. Nat. Protoc. 16, 3802–3835 (2021). 34215862 PMC8647621 · DOI
  110. [121]Risom, T. et al. Transition to invasive breast cancer is associated with progressive changes in the structure and composition of tumor stroma. Cell 185, 299–310 e218 (2022). 35063072 PMC8792442 · DOI
  111. [124]Luca, B. A. et al. Atlas of clinically distinct cell states and ecosystems across human solid tumors. Cell 184, 5482–5496.e5428 (2021). 34597583 PMC8526411 · DOI
  112. [125]Chen, W. et al. Live-seq enables temporal transcriptomic recording of single cells. Nature 608, 733–740 (2022). 35978187 PMC9402441 · DOI
  113. [126]Cai, S. et al. Spatially resolved subcellular protein-protein interactomics in drug-perturbed lung-cancer cultures and tissues. Nat. Biomed. Eng. 10.1038/s41551-024-01271-x (2024). PMC12707392 39478233 · DOI
  114. [127]Enfield, K. S. S. et al. Spatial Architecture of Myeloid and T Cells Orchestrates Immune Evasion and Clinical Outcome in Lung Cancer. Cancer Discov. 14, 1018–1047 (2024). 38581685 PMC11145179 · DOI
  115. [128]Hiltbrunner, S. et al. Acquired resistance to anti-PD1 therapy in patients with NSCLC associates with immunosuppressive T cell phenotype. Nat. Commun. 14, 5154 (2023). 37620318 PMC10449840 · DOI
  116. [129]Sorin, M. et al. Single-cell spatial landscapes of the lung tumour immune microenvironment. Nature 614, 548–554 (2023). 36725934 PMC9931585 · DOI
  117. [130]Bressan, D., Battistoni, G. & Hannon, G. J. The dawn of spatial omics. Science 381, eabq4964 (2023). 37535749 PMC7614974 · DOI
  118. [131]Zhang, Y. W., Gvozdenovic, A. & Aceto, N. A Molecular Voyage: Multiomics Insights into Circulating Tumor Cells. Cancer Discov. 14, 920–933 (2024). 38581442 · DOI
  119. [132]Passaro, A. et al. Cancer biomarkers: Emerging trends and clinical implications for personalized treatment. Cell 187, 1617–1635 (2024). 38552610 PMC7616034 · DOI
  120. [133]Di Federico, A. et al. Predictors of survival to immunotherapy and chemoimmunotherapy in non-small cell lung cancer: A meta-analysis. J. Natl. Cancer Inst. 115, 29–42 (2023). 36322815 · DOI
  121. [134]Akhoundova, D. & Rubin, M. A. Clinical application of advanced multi-omics tumor profiling: Shaping precision oncology of the future. Cancer Cell 40, 920–938 (2022). 36055231 · DOI
  122. [135]Conn, V. M., Chinnaiyan, A. M. & Conn, S. J. Circular RNA in cancer. Nat. Rev. Cancer 24, 597–613 (2024). 39075222 · DOI
  123. [136]Peters, S. et al. Entrectinib in ROS1-positive advanced non-small cell lung cancer: the phase 2/3 BFAST trial. Nat. Med. 30, 1923–1932 (2024). 38898120 PMC11271410 · DOI
  124. [137]Lawrence, R. et al. Circulating tumour cells for early detection of clinically relevant cancer. Nat. Rev. Clin. Oncol. 20, 487–500 (2023). 37268719 PMC10237083 · DOI
  125. [138]Coombs, C. C. et al. Therapy-Related Clonal Hematopoiesis in Patients with Non-hematologic Cancers Is Common and Associated with Adverse Clinical Outcomes. Cell Stem Cell 21, 374–382.e374 (2017). 28803919 PMC5591073 · DOI · Paper page
  126. [139]Gouda, M. A. et al. Liquid Biopsy Response Evaluation Criteria in Solid Tumors (LB-RECIST). Ann. Oncol. 35, 267–275 (2024). 38145866 · DOI
  127. [140]Tan, A. C. et al. Detection of circulating tumor DNA with ultradeep sequencing of plasma cell-free DNA for monitoring minimal residual disease and early detection of recurrence in early-stage lung cancer. Cancer 130, 1758–1765 (2024). 38422026 · DOI
  128. [141]Anagnostou, V. et al. ctDNA response after pembrolizumab in non-small cell lung cancer: phase 2 adaptive trial results. Nat. Med. 29, 2559–2569 (2023). 37814061 PMC10579094 · DOI
  129. [142]Widman, A. J. et al. Ultrasensitive plasma-based monitoring of tumor burden using machine-learning-guided signal enrichment. Nat. Med. 30, 1655–1666 (2024). 38877116 PMC7616143 · DOI
  130. [143]Dall’Olio, F. G. et al. PD-L1 Expression in Circulating Tumor Cells as a Promising Prognostic Biomarker in Advanced Non-small-cell Lung Cancer Treated with Immune Checkpoint Inhibitors. Clin. Lung Cancer 22, 423–431 (2021). 33849808 · DOI
  131. [144]Lu, M. Y. et al. AI-based pathology predicts origins for cancers of unknown primary. Nature 594, 106–110 (2021). 33953404 · DOI · Paper page
  132. [145]Shreenivas, A. V. et al. Carcinoma of unknown primary: Molecular tumor board-based therapy. CA Cancer J. Clin. 72, 510–523 (2022). 36006378 PMC10180180 · DOI
  133. [146]Zheng, R. et al. Molecular profiling of key driver genes improves staging accuracy in multifocal non-small cell lung cancer. J. Thorac. Cardiovasc. Surg. 160, e71–e79 (2020). 32007245 · DOI
  134. [147]Karimzadeh, M. et al. Deep generative AI models analyzing circulating orphan non-coding RNAs enable detection of early-stage lung cancer. Nat. Commun. 15, 10090 (2024). 39572521 PMC11582319 · DOI
  135. [148]Medford, A. J. et al. A standing platform for cancer drug development using ctDNA-based evidence of recurrence. Nat. Rev. Cancer 24, 810–821 (2024). 39349822 · DOI
  136. [149]Herbst, R. S. et al. Adjuvant Osimertinib for Resected EGFR-Mutated Stage IB-IIIA Non-Small-Cell Lung Cancer: Updated Results From the Phase III Randomized ADAURA Trial. J. Clin. Oncol. 41, 1830–1840 (2023). 36720083 PMC10082285 · DOI
  137. [150]Piper, M., Kluger, H., Ruppin, E. & Hu-Lieskovan, S. Immune Resistance Mechanisms and the Road to Personalized Immunotherapy. Am. Soc. Clin. Oncol. Educ. Book 43, e390290 (2023). 37459578 · DOI
  138. [151]Bessede, A. et al. TROP2 Is Associated with Primary Resistance to Immune Checkpoint Inhibition in Patients with Advanced Non-Small Cell Lung Cancer. Clin. Cancer Res. 30, 779–785 (2024). 38048058 PMC10870116 · DOI
  139. [152]Alessi, J. V. et al. Impact of Aneuploidy and Chromosome 9p Loss on Tumor Immune Microenvironment and Immune Checkpoint Inhibitor Efficacy in NSCLC. J. Thorac. Oncol. 18, 1524–1537 (2023). 37247843 PMC10913104 · DOI
  140. [153]Wang, J., Fan, X., Zhang, J. & Huang, C. Clinical value of peripheral blood circulating tumor DNA in predicting the efficacy of immunotherapy for non-small cell lung cancer. J. Thorac. Dis. 15, 2659–2667 (2023). 37324075 PMC10267936 · DOI
  141. [154]Teillaud, J. L. et al. Tertiary lymphoid structures in anticancer immunity. Nat. Rev. Cancer 24, 629–646 (2024). 39117919 · DOI
  142. [157]Doroshow, D. B. et al. PD-L1 as a biomarker of response to immune-checkpoint inhibitors. Nat. Rev. Clin. Oncol. 18, 345–362 (2021). 33580222 · DOI · Paper page
  143. [158]Oh, S. A. et al. PD-L1 expression by dendritic cells is a key regulator of T-cell immunity in cancer. Nat. Cancer 1, 681–691 (2020). 35122038 · DOI
  144. [159]Gohil, S. H. et al. Applying high-dimensional single-cell technologies to the analysis of cancer immunotherapy. Nat. Rev. Clin. Oncol. 18, 244–256 (2021). 33277626 PMC8415132 · DOI · Paper page
  145. [160]Laumont, C. M. et al. Global proteogenomic analysis of human MHC class I-associated peptides derived from non-canonical reading frames. Nat. Commun. 7, 10238 (2016). 26728094 PMC4728431 · DOI
  146. [161]Abbosh, C. et al. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature 545, 446–451 (2017). 28445469 PMC5812436 · DOI
  147. [162]Mino-Kenudson, M. et al. Predictive Biomarkers for Immunotherapy in Lung Cancer: Perspective From the International Association for the Study of Lung Cancer Pathology Committee. J. Thorac. Oncol. 17, 1335–1354 (2022). 36184066 · DOI
  148. [163]Paijens, S. T., Vledder, A., de Bruyn, M. & Nijman, H. W. Tumor-infiltrating lymphocytes in the immunotherapy era. Cell Mol. Immunol. 18, 842–859 (2021). 33139907 PMC8115290 · DOI
  149. [164]Kwong, G. A. et al. Synthetic biomarkers: a twenty-first century path to early cancer detection. Nat. Rev. Cancer 21, 655–668 (2021). 34489588 PMC8791024 · DOI
  150. [165]Kroemer, G., Chan, T. A., Eggermont, A. M. M. & Galluzzi, L. Immunosurveillance in clinical cancer management. CA Cancer J. Clin. 74, 187–202 (2024). 37880100 PMC10939974 · DOI
  151. [166]Nabet, B. Y. et al. Noninvasive Early Identification of Therapeutic Benefit from Immune Checkpoint Inhibition. Cell 183, 363–376.e313 (2020). 33007267 PMC7572899 · DOI
  152. [167]Wang, K. et al. Deconvolving Clinically Relevant Cellular Immune Cross-talk from Bulk Gene Expression Using CODEFACS and LIRICS Stratifies Patients with Melanoma to Anti-PD-1 Therapy. Cancer Discov. 12, 1088–1105 (2022). 34983745 PMC8983586 · DOI
  153. [168]Price, J. M., Prabhakaran, A. & West, C. M. L. Predicting tumour radiosensitivity to deliver precision radiotherapy. Nat. Rev. Clin. Oncol. 20, 83–98 (2023). 36477705 · DOI
  154. [169]Horne, A. et al. Treatment Response Biomarkers: Working Toward Personalized Radiotherapy for Lung Cancer. J. Thorac. Oncol. 19, 1164–1185 (2024). 38615939 · DOI
  155. [170]Galluzzi, L. et al. Targeting immunogenic cell stress and death for cancer therapy. Nat. Rev. Drug Discov. 23, 445–460 (2024). 38622310 PMC11153000 · DOI
  156. [171]Chang, H. H. Y., Pannunzio, N. R., Adachi, N. & Lieber, M. R. Non-homologous DNA end joining and alternative pathways to double-strand break repair. Nat. Rev. Mol. Cell Biol. 18, 495–506 (2017). 28512351 PMC7062608 · DOI · Paper page
  157. [172]Mohammadi, H. et al. Using the Radiosensitivity Index (RSI) to Predict Pelvic Failure in Endometrial Cancer Treated With Adjuvant Radiation Therapy. Int. J. Radiat. Oncol. Biol. Phys. 106, 496–502 (2020). 31759077 PMC7050205 · DOI
  158. [173]Han, F. et al. Targeting Nrf2/PHKG2 axis to enhance radiosensitivity in NSCLC. NPJ Precis. Oncol. 8, 183 (2024). 39169204 PMC11339382 · DOI
  159. [174]Chiang, J. C. et al. Lipoylation inhibition enhances radiation control of lung cancer by suppressing homologous recombination DNA damage repair. Sci Adv. 11, eadt1241 (2025). 40073141 PMC11900879 · DOI
  160. [175]Ko, E. C., Raben, D. & Formenti, S. C. The Integration of Radiotherapy with Immunotherapy for the Treatment of Non-Small Cell Lung Cancer. Clin. Cancer Res. 24, 5792–5806 (2018). 29945993 · DOI
  161. [176]Mooradian, M. J. et al. Durvalumab After Chemoradiotherapy in Patients With Unresectable Stage III Non-Small Cell Lung Cancer. JAMA Netw. Open 7, e247542 (2024). 38648057 PMC11036139 · DOI
  162. [177]Someya, M. et al. Radiotherapy for HPV-related cancers: prediction of therapeutic effects based on the mechanism of tumor immunity and the application of immunoradiotherapy. Jpn J. Radio. 40, 458–465 (2022). PMC9068647 34973113 · DOI
  163. [178]Vanpouille-Box, C. et al. TGFbeta Is a Master Regulator of Radiation Therapy-Induced Antitumor Immunity. Cancer Res. 75, 2232–2242 (2015). 25858148 PMC4522159 · DOI · Paper page
  164. [179]Ascione, L. et al. Unlocking the Potential: Biomarkers of Response to Antibody-Drug Conjugates. Am. Soc. Clin. Oncol. Educ. Book 44, e431766 (2024). 38828973 · DOI
  165. [180]Marra, A., Chandarlapaty, S. & Modi, S. Management of patients with advanced-stage HER2-positive breast cancer: current evidence and future perspectives. Nat. Rev. Clin. Oncol. 21, 185–202 (2024). 38191924 PMC12327481 · DOI
  166. [181]Li, B. T. et al. Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer. N. Engl. J. Med. 386, 241–251 (2022). 34534430 PMC9066448 · DOI
  167. [182]Dumontet, C. et al. Antibody-drug conjugates come of age in oncology. Nat. Rev. Drug Discov. 22, 641–661 (2023). 37308581 · DOI
  168. [183]Abuhelwa, Z., Alloghbi, A. & Nagasaka, M. A comprehensive review on antibody-drug conjugates (ADCs) in the treatment landscape of non-small cell lung cancer (NSCLC). Cancer Treat. Rev. 106, 102393 (2022). 35472631 PMC12582167 · DOI
  169. [185]Sujit, S. J. et al. Enhancing NSCLC recurrence prediction with PET/CT habitat imaging, ctDNA, and integrative radiogenomics-blood insights. Nat. Commun. 15, 3152 (2024). 38605064 PMC11009351 · DOI
  170. [187]Wang, X. et al. A pathology foundation model for cancer diagnosis and prognosis prediction. Nature 634, 970–978 (2024). 39232164 PMC12186853 · DOI · Paper page
  171. [188]Zhao, J. et al. Health insurance status and cancer stage at diagnosis and survival in the United States. CA Cancer J. Clin. 72, 542–560 (2022). 35829644 · DOI
  172. [189]Provencio, M. et al. Treatment Sequencing in Resectable Lung Cancer: The Good and the Bad of Adjuvant Versus Neoadjuvant Therapy. Am. Soc. Clin. Oncol. Educ. Book 42, 1–18 (2022). 35561296
  173. [192]Donington, J., Schumacher, L. & Yanagawa, J. Surgical Issues for Operable Early-Stage Non-Small-Cell Lung Cancer. J. Clin. Oncol. 40, 530–538 (2022). 34985938 · DOI
  174. [193]Bian, D. et al. Neoadjuvant Afatinib for stage III EGFR-mutant non-small cell lung cancer: a phase II study. Nat. Commun. 14, 4655 (2023). 37537219 PMC10400609 · DOI
  175. [194]Spicer, J. D. et al. Multimodality Therapy for N2 Non-Small Cell Lung Cancer: An Evolving Paradigm. Ann. Thorac. Surg. 107, 277–284 (2019). 30227129 PMC6993842 · DOI
  176. [195]Mountzios, G. et al. Immune-checkpoint inhibition for resectable non-small-cell lung cancer - opportunities and challenges. Nat. Rev. Clin. Oncol. 20, 664–677 (2023). 37488229 · DOI
  177. [196]Provencio, M. et al. Perioperative chemotherapy and nivolumab in non-small-cell lung cancer (NADIM): 5-year clinical outcomes from a multicentre, single-arm, phase 2 trial. Lancet Oncol. 25, 1453–1464 (2024). 39419061 PMC11519011 · DOI
  178. [197]Provencio, M. et al. Perioperative Nivolumab and Chemotherapy in Stage III Non-Small-Cell Lung Cancer. N. Engl. J. Med. 389, 504–513 (2023). 37379158 · DOI
  179. [198]Mitsudomi, T. et al. Neoadjuvant nivolumab plus chemotherapy in resectable non-small-cell lung cancer in Japanese patients from CheckMate 816. Cancer Sci. 115, 540–554 (2024). 38098261 PMC10859619 · DOI
  180. [199]Zhang, P. et al. Neoadjuvant Sintilimab and Chemotherapy for Resectable Stage IIIA Non-Small Cell Lung Cancer. Ann. Thorac. Surg. 114, 949–958 (2022). 35176262 · DOI
  181. [200]Shu, C. A. et al. Neoadjuvant atezolizumab and chemotherapy in patients with resectable non-small-cell lung cancer: an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol. 21, 786–795 (2020). 32386568 · DOI · Paper page
  182. [202]Lu, S. et al. Perioperative Toripalimab Plus Chemotherapy for Patients With Resectable Non-Small Cell Lung Cancer: The Neotorch Randomized Clinical Trial. JAMA 331, 201–211 (2024). 38227033 PMC10792477 · DOI
  183. [203]Cascone, T. et al. Perioperative Nivolumab in Resectable Lung Cancer. N. Engl. J. Med. 390, 1756–1769 (2024). 38749033 · DOI
  184. [204]Heymach, J. V. et al. Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer. N. Engl. J. Med. 389, 1672–1684 (2023). 37870974 · DOI
  185. [205]Yang, Z. et al. Treatment patterns and clinical outcomes of patients with resectable non-small cell lung cancer receiving neoadjuvant immunochemotherapy: A large-scale, multicenter, real-world study (NeoR-World). J. Thorac. Cardiovasc. Surg. 168, 1245–1258.e1217 (2024). 38342430 · DOI
  186. [206]Adachi, H. et al. Effect of Surgical Treatment for N2-Positive c-stage III Non-Small Cell Lung Carcinoma in the “PACIFIC” Era. Clin. Lung Cancer 24, 733–742 (2023). 37543472 · DOI
  187. [207]De Leyn, P. et al. Survival after trimodality treatment for superior sulcus and central T4 non-small cell lung cancer. J. Thorac. Oncol. 4, 62–68 (2009). 19096308 · DOI
  188. [208]Paul, S. et al. Survival of patients with clinical stage IIIA non-small cell lung cancer after induction therapy: age, mediastinal downstaging, and extent of pulmonary resection as independent predictors. J. Thorac. Cardiovasc. Surg. 141, 48–58 (2011). 21092990 · DOI
  189. [209]Tang, A. et al. Robotic Approach Offers Similar Nodal Upstaging to Open Lobectomy for Clinical Stage I Non-small Cell Lung Cancer. Ann. Thorac. Surg. 110, 424–433 (2020). 32240644 · DOI
  190. [210]Tsutani, Y. et al. Oncologic outcomes of segmentectomy compared with lobectomy for clinical stage IA lung adenocarcinoma: propensity score-matched analysis in a multicenter study. J. Thorac. Cardiovasc. Surg. 146, 358–364 (2013). 23477694 · DOI
  191. [211]Raman, V. et al. The Effect of Tumor Size and Histologic Findings on Outcomes After Segmentectomy vs Lobectomy for Clinically Node-Negative Non-Small Cell Lung Cancer. Chest 159, 390–400 (2021). 32652096 PMC7856530 · DOI
  192. [212]Rogers, L. J. et al. The impact of enhanced recovery after surgery (ERAS) protocol compliance on morbidity from resection for primary lung cancer. J. Thorac. Cardiovasc. Surg. 155, 1843–1852 (2018). 29352586 · DOI
  193. [213]Zhou, R. et al. Fraction Dose Escalation of Hypofractionated Radiotherapy with Concurrent Chemotherapy and Subsequent Consolidation Immunotherapy in Locally Advanced Non-Small Cell Lung Cancer: A Phase I Study. Clin. Cancer Res. 30, 2719–2728 (2024). 38652815 · DOI
  194. [214]Lu, S. et al. Osimertinib after Chemoradiotherapy in Stage III EGFR-Mutated NSCLC. N. Engl. J. Med. 391, 585–597 (2024). 38828946 · DOI
  195. [215]Schuler, M. et al. Neoadjuvant nivolumab with or without relatlimab in resectable non-small-cell lung cancer: a randomized phase 2 trial. Nat. Med. 30, 1602–1611 (2024). 38689060 PMC11186754 · DOI
  196. [216]Tachihara, M. et al. Durvalumab Plus Concurrent Radiotherapy for Treatment of Locally Advanced Non-Small Cell Lung Cancer: The DOLPHIN Phase 2 Nonrandomized Controlled Trial. JAMA Oncol. 9, 1505–1513 (2023). 37676681 PMC10485744 · DOI
  197. [217]Monjazeb, A. M. et al. Atezolizumab plus stereotactic ablative radiotherapy for medically inoperable patients with early-stage non-small cell lung cancer: a multi-institutional phase I trial. Nat. Commun. 14, 5332 (2023). 37658083 PMC10474145 · DOI
  198. [218]Yamada, T. et al. A phase 2 trial of durvalumab treatment following radiation monotherapy in patients with non-small cell lung cancer ineligible for stage III chemoradiotherapy: The SPIRAL-RT study. Eur. J. Cancer 195, 113373 (2023). 37890349 · DOI
  199. [219]Xia, H. et al. Neoadjuvant camrelizumab (an anti-PD-1 antibody) plus chemotherapy or apatinib (a VEGFR-2 inhibitor) for initially unresectable stage II-III non-small-cell lung cancer: a multicentre, two-arm, phase 2 exploratory study. Sig. Transduct. Target Ther. 9, 145 (2024). PMC11176298 38871690 · DOI
  200. [220]Rimner, A. et al. Stereotactic Body Radiation Therapy for Stage IIA to IIIA Inoperable Non-Small Cell Lung Cancer: A Phase 1 Dose-Escalation Trial. Int. J. Radiat. Oncol. Biol. Phys. 119, 869–877 (2024). 38154510 PMC12094679 · DOI

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Cited by

Sorted by citations

Authors
Huang, Q., Li, Y., Huang, Y., Wu, J., Bao, W., Xue, C., Li, X., Dong, S., Dong, Z., & Hu, S.
Affiliations
  • Hubei Cancer Hospital (CN)
  • Hubei University of Medicine (CN)
Corresponding author
  • Dong, Zhiqiang
  • Hu, Sheng
ORCID
Venue
Signal Transduction and Targeted Therapy
Publisher
Springer Science and Business Media LLC
Published
2025-06-15
Volume
10
Issue
1
Pages
186-186
ISSN
2059-3635 (ISSN-L)
DOI
10.1038/s41392-025-02243-6
PMC
PMC12167388
OpenAlex
W4411302254
Cited by
197
References
79
Citations by year
2026: 167 · 2025: 30
FWCI
34.25
Type
journal article
Language
en
Open access
Licence
Locations
  • Signal Transduction and Targeted Therapy (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
  • Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
Keywords
non-small cell lung cancer, molecular pathology, metastasis mechanisms, therapeutic target, spatial omics, small molecule drugs, antibody drugs, combination therapy, drug resistance, targeted therapy, immunotherapy, artificial intelligence, clinical translation
MeSH terms
Carcinoma, Non-Small-Cell Lung, Humans, Immunotherapy, Lung Neoplasms, Drug Resistance, Neoplasm, Molecular Targeted Therapy

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