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Immunotherapy has delivered only limited gains for a small metastatic subset, while relapse in extended-disease SCLC continues to show scarce options. Growing molecular characterization has revealed key signaling pathways, enabling identification of actionable targets. Despite many tested agents and frequent failures, emerging targeted therapies show preliminary promise; this review summarizes the principal pathways and current targeted strategies under investigation.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/targeted-therapies-in-small-cell-lung-cancer-from-old-failures-to-novel-therapeutic-strategies/383648/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/targeted-therapies-in-small-cell-lung-cancer-from-old-failures-to-novel-therapeutic-strategies/383648.png","ImageObject",300,407,{"name":92,"@type":93},"River Wang","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-02","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is treatment of small cell lung cancer considered challenging?","Question",{"text":112,"@type":113},"SCLC has few impactful therapeutic advances, and most relapsed or extended-disease settings remain difficult to treat. Prognosis is poor with aggressive disease biology and limited survival.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What impact has immunotherapy had in SCLC care?",{"text":117,"@type":113},"Immunotherapy produced marginal benefit for a limited subset of metastatic patients, improving outcomes only modestly compared with chemotherapy alone. In many relapsed settings, checkpoint inhibitor trials have been disappointing overall.",{"name":119,"@type":110,"acceptedAnswer":120},"How do targeted therapies fit into the newer SCLC strategy?",{"text":121,"@type":113},"Molecular profiling has clarified signaling pathways involved in SCLC development and progression, supporting identification of potential clinical targets. Several targeted approaches have shown preliminary results despite many prior therapeutic failures.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},383648,1791101827,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},1099514067438,"https://ap-avatar.wpscdn.com/avatar/100002539ee87300030?x-image-process=image/resize,m_fixed,w_180,h_180&k=1780474512215547542","Review  \nTargeted Therapies in Small Cell Lung Cancer: From Old Failures to Novel Therapeutic Strategies  \nMassimiliano Cani†, Valerio Maria Napoli†, Edoardo Garbo, Giorgia Ferrari , Benedetta Del Rio , Silvia Novello and Francesco Passiglia *  \nDepartment of Oncology, University of Turin, San Luigi Hospital, 10043 Orbassano, TO, Italy;  \nmassimiliano.cani@unito.it (M.C.); [valeriomaria.napoli@gmail.com](valeriomaria.napoli@gmail.com) (V.M.N.); edoardo.garbo@unito.it (E.G.);  \n[giorgia.ferrari@unito.it](giorgia.ferrari@unito.it) (G.F.); benedetta.delrio@unito.it (B.D.R.); silvia.novello@unito.it (S.N.)  \n* Correspondence: francesco.passiglia@unito.it  \n† These authors contributed equally to this work.  \nAbstract: The clinical management of small cell lung cancer (SCLC) treatment remains a major challenge for thoracic oncologists, with very few therapeutic advances significantly impacting patients'survival. The recent introduction of immunotherapy in the clinical setting produced a marginal benefit for a limited subset of metastatic patients, while the therapeutic scenario for relapsing extended-disease small cell lung cancers (ED-SCLCs) remains almost deserted. Recent efforts clarified the molecular features of this disease, leading to the identification of key signalling pathways which may serve as potential targets for clinical use. Despite the large number of molecules tested and the numerous therapeutic failures, some targeted therapies have recently shown interesting preliminary results. In this review, we describe the main molecular pathways involved in SCLC development/progression and provide an updated summary of the targeted therapies currently under investigation in SCLC patients.  \nCitation: Cani, M.; Napoli, V.M.; Garbo, E.; Ferrari, G.; Del Rio, B.; Novello, S.; Passiglia, F. Targeted Therapies in Small Cell Lung Cancer:  \nFrom Old Failures to Novel Therapeutic Strategies. Int. J. Mol. Sci. 2023, 24, 8883. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms24108883](10.3390/ijms24108883)  \nAcademic Editor: Robert Arthur Kratzke  \nReceived: 2 May 2023  \nRevised: 13 May 2023  \nAccepted: 15 May 2023  \nPublished: 17 May 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \nKeywords: targeted therapies; small cell lung cancer; SCLC  \n1. Introduction  \nSmall cell lung cancer (SCLC) is a high-grade neuroendocrine tumour accounting for 15% of lung malignant neoplasms. Lung neuroendocrine tumours have been categorised as a single group of neoplasms since 2015, while the most recent 2021 World Health Organization (WHO) classification includes low-grade typical carcinoid (TC), intermediate atypical carcinoid (AC) and high-grade subtypes, such as small cell lung cancer (SCLC) and large cell neuroendocrine cancers (LCNEC) [1,2] . Globally, 250,000 new diagnosesand 200,000 deaths from SCLC are expected every year, with a higher prevalence in highincome countries, especially among men [3] . Over the latest 30 years, SCLC incidence decreased in the overall US population as a result of tobacco attitude reduction, thus reinforcing the strong link between tobacco consumption and SCLC occurrence. Recently a higher proportion of diagnoses have been reported among female and elderly patients, increasing from 23% in 1975 to 44% in 2010 [4] . Beyond tobacco smoking history [5], other risk factors include both air pollution and radon exposure, even if the evidence is still weak [3]. Although lung cancer screening programmes by low-dose computed tomography (CT) demonstrated a significant reduction of lung cancer-related mortality in the high-risk smoking population, no benefit was proven in SCLC disease [6–8] . Based on ","cbCaihvetF7ITdPy","https://ap.wps.com/l/cbCaihvetF7ITdPy","pdf",902692,22,"English","# Introduction\n## Burden and biology of SCLC\n## Current treatment landscape and clinical outcomes\n# Molecular features and potential therapeutic targets\n# Targeted therapies under investigation\n# Conclusion","[{\"question\":\"Why is treatment of small cell lung cancer considered challenging?\",\"answer\":\"SCLC has few impactful therapeutic advances, and most relapsed or extended-disease settings remain difficult to treat. Prognosis is poor with aggressive disease biology and limited survival.\"},{\"question\":\"What impact has immunotherapy had in SCLC care?\",\"answer\":\"Immunotherapy produced marginal benefit for a limited subset of metastatic patients, improving outcomes only modestly compared with chemotherapy alone. In many relapsed settings, checkpoint inhibitor trials have been disappointing overall.\"},{\"question\":\"How do targeted therapies fit into the newer SCLC strategy?\",\"answer\":\"Molecular profiling has clarified signaling pathways involved in SCLC development and progression, supporting identification of potential clinical targets. Several targeted approaches have shown preliminary results despite many prior therapeutic failures.\"}]","Targeted Therapies in Small Cell Lung Cancer: From Old Failures to Novel Therapeutic Strategies | PDF",1790258557,55]