Sutherland KD, Ireland AS, Oliver TG. Killing SCLC: insights into how to target a shapeshifting tumor. Genes Dev. 2022;36:241–58.

Article  CAS  PubMed  PubMed Central  Google Scholar 

George J, Lim JS, Jang SJ, Cun Y, Ozretic L, Kong G, et al. Comprehensive genomic profiles of small cell lung cancer. Nature. 2015;524:47–53.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rudin CM, Durinck S, Stawiski EW, Poirier JT, Modrusan Z, Shames DS, et al. Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer. Nat Genet. 2012;44:1111–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Baine MK, Hsieh MS, Lai WV, Egger JV, Jungbluth AA, Daneshbod Y, et al. SCLC subtypes defined by ASCL1, NEUROD1, POU2F3, and YAP1: a comprehensive immunohistochemical and histopathologic characterization. J Thorac Oncol. 2020;15:1823–35.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gay CM, Stewart CA, Park EM, Diao L, Groves SM, Heeke S, et al. Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities. Cancer Cell. 2021;39:346–e360347.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rudin CM, Poirier JT, Byers LA, Dive C, Dowlati A, George J, et al. Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data. Nat Rev Cancer. 2019;19:289–97.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Abdel Karim NF, Miao J, Reckamp KL, Gay CM, Byers LA, Zhao Y, et al. SWOG S1929: phase II randomized study of maintenance atezolizumab (A) versus atezolizumab + talazoparib (AT) in patients with SLFN11 positive extensive stage small cell lung cancer (ES-SCLC). J Clin Oncol. 2023;41:8504.

Article  Google Scholar 

Ganti AKP, Loo BW, Bassetti M, Blakely C, Chiang A, D’Amico TA, et al. Small cell lung cancer, version 2.2022, NCCN Clinical Practice guidelines in Oncology. J Natl Compr Canc Netw. 2021;19:1441–64.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019;394:1929–39.

Article  CAS  PubMed  Google Scholar 

Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, et al. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021;22:51–65.

Article  CAS  PubMed  Google Scholar 

Paz-Ares L, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, et al. Durvalumab, with or without tremelimumab, plus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer: 3-year overall survival update from CASPIAN. ESMO Open. 2022;7:100408.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Devarakonda S, Sankararaman S, Herzog BH, Gold KA, Waqar SN, Ward JP, et al. Circulating tumor DNA profiling in small-cell lung cancer identifies potentially targetable alterations. Clin Cancer Res. 2019;25:6119–26.

Article  CAS  PubMed  PubMed Central  Google Scholar 

So WV, Dejardin D, Rossmann E, Charo J. Predictive biomarkers for PD-1/PD-L1 checkpoint inhibitor response in NSCLC: an analysis of clinical trial and real-world data. J Immunother Cancer. 2023;11:e006464.

Article  PubMed  PubMed Central  Google Scholar 

Kasmann L, Nieto A, Taugner J, Manapov F. PD-L1 expression on tumor cells as a potential predictive biomarker for patients with unresectable stage III non-small cell lung cancer treated with chemoradiotherapy followed by durvalumab. Transl Cancer Res. 2023;12:705–8.

Article  PubMed  PubMed Central  Google Scholar 

Khan M, Du K, Ai M, Wang B, Lin J, Ren A, et al. PD-L1 expression as biomarker of efficacy of PD-1/PD-L1 checkpoint inhibitors in metastatic triple negative breast cancer: a systematic review and meta-analysis. Front Immunol. 2023;14:1060308.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Paz-Ares L, Garassino MC, Chen Y, Reinmuth N, Hotta K, Poltoratskiy A, et al. Durvalumab ± tremelimumab + platinum-etoposide in extensive-stage small cell Lung Cancer (CASPIAN): outcomes by PD-L1 expression and tissue Tumor Mutational Burden. Clin Cancer Res. 2024;30:824–35.

Article  PubMed  Google Scholar 

Liu SV, Reck M, Mansfield AS, Mok T, Scherpereel A, Reinmuth N, et al. Updated overall survival and PD-L1 subgroup analysis of patients with extensive-stage small-cell lung cancer treated with atezolizumab, carboplatin, and etoposide (IMpower133). J Clin Oncol. 2021;39:619–30.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Horn L, Mansfield AS, Szczesna A, Havel L, Krzakowski M, Hochmair MJ, et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018;379:2220–9.

Article  CAS  PubMed  Google Scholar 

Rudin CM, Kim HR, Navarro A, Gottfried M, Peters S, Csoszi T, et al. Exploratory biomarker analysis of the phase 3 KEYNOTE-604 study of pembrolizumab plus etoposide for extensive-stage SCLC. J Clin Oncol. 2023;41:8503.

Article  Google Scholar 

Rudin CM, Awad MM, Navarro A, Gottfried M, Peters S, Csoszi T, et al. Pembrolizumab or placebo plus etoposide and platinum as first-line therapy for extensive-stage small-cell lung cancer: randomized, double-blind, phase III KEYNOTE-604 study. J Clin Oncol. 2020;38:2369–79.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rudin CM, Balli D, Lai WV, Richards AL, Nguyen E, Egger JV et al. Clinical benefit from immunotherapy in patients with small cell lung cancer is associated with tumor capacity for antigen presentation. J Thorac Oncol. 2023:1222–32.

Owonikoko TK, Dwivedi B, Chen Z, Zhang C, Barwick B, Ernani V, et al. YAP1 expression in SCLC defines a distinct subtype with T-cell-inflamed phenotype. J Thorac Oncol. 2021;16:464–76.

Article  CAS  PubMed  Google Scholar 

Ayers M, Lunceford J, Nebozhyn M, Murphy E, Loboda A, Kaufman DR, et al. IFN-gamma-related mRNA profile predicts clinical response to PD-1 blockade. J Clin Invest. 2017;127:2930–40.

Article  PubMed  PubMed Central  Google Scholar 

Qu S, Fetsch P, Thomas A, Pommier Y, Schrump DS, Miettinen MM, et al. Molecular subtypes of primary SCLC tumors and their associations with neuroendocrine and therapeutic markers. J Thorac Oncol. 2022;17:141–53.

Article  CAS  PubMed  Google Scholar 

Mahadevan NR, Knelson EH, Wolff JO, Vajdi A, Saigi M, Campisi M, et al. Intrinsic immunogenicity of small cell lung carcinoma revealed by its cellular plasticity. Cancer Discov. 2021;11:1952–69.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rooney MS, Shukla SA, Wu CJ, Getz G, Hacohen N. Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell. 2015;160:48–61.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chalmers ZR, Connelly CF, Fabrizio D, Gay L, Ali SM, Ennis R, et al. Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med. 2017;9:34.

Article  PubMed  PubMed Central  Google Scholar 

Rizvi NA, Cho BC, Reinmuth N, Lee KH, Luft A, Ahn MJ, et al. Durvalumab with or without tremelimumab vs standard chemotherapy in first-line treatment of metastatic non-small cell lung cancer: the MYSTIC phase 3 randomized clinical trial. JAMA Oncol. 2020;6:661–74.

Article  PubMed  PubMed Central  Google Scholar 

de Castro G Jr., Rizvi NA, Schmid P, Syrigos K, Martin C, Yamamoto N, et al. NEPTUNE: phase 3 study of first-line durvalumab plus tremelimumab in patients with metastatic NSCLC. J Thorac Oncol. 2023;18:106–19.

Article  PubMed  Google Scholar 

Megyesfalvi Z, Barany N, Lantos A, Valko Z, Pipek O, Lang C, et al. Expression patterns and prognostic relevance of subtype-specific transcription factors in surgically resected small-cell lung cancer: an international multicenter study. J Pathol. 2022;257:674–86.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Burr ML, Sparbier CE, Chan KL, Chan YC, Kersbergen A, Lam EYN, et al. An evolutionarily conserved function of polycomb silences the MHC class I antigen presentation pathway and enables immune evasion in cancer. Cancer Cell. 2019;36:385–e401388.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nguyen EM, Taniguchi H, Chan JM, Zhan YA, Chen X, Qiu J, et al. Targeting lysine-specific demethylase 1 rescues major histocompatibility complex class I antigen presentation and overcomes programmed death-ligand 1 blockade resistance in SCLC. J Thorac Oncol. 2022;17:1014–31.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hiatt JB, Sandborg H, Garrison SM, Arnold HU, Liao SY, Norton JP, et al. Inhibition of LSD1 with bomedemstat sensitizes small cell lung cancer to immune checkpoint blockade and T-cell killing. Clin Cancer Res. 2022;28:4551–64.

Article  CAS  PubMed  PubMed Central