Cancer treatment reviews最新文献

{"title":"Recommendations on the management of kinase inhibitor-associated hyperlipidemia in patients with lung cancer","authors":"Hung-Ju Lin ,&nbsp;Shang-Gin Wu ,&nbsp;Yin Lo ,&nbsp;Po-Hao Feng ,&nbsp;Yen-Wen Wu ,&nbsp;Kuan-Yu Chen","doi":"10.1016/j.ctrv.2025.103065","DOIUrl":"10.1016/j.ctrv.2025.103065","url":null,"abstract":"<div><h3>Introduction</h3><div>Kinase inhibitors (KIs) play an important role in targeted therapy for lung cancer. Lorlatinib as a third-generation anaplastic lymphoma kinase (ALK) inhibitor, provided unprecedentedly prolonged survival for patients with advanced non-small cell lung cancer harboring <em>ALK</em> rearrangements. However, this benefit comes at a cost of hyperlipidemia with possible implications for cardiovascular disease (CVD) in long-term survivors. This review aims to provide multidisciplinary evidence-based recommendations for managing hyperlipidemia related to KIs.</div></div><div><h3>Methods</h3><div>We established a collaborative study group comprising cardiologists, thoracic oncologists, and a pharmacist. The working group conducted a comprehensive literature search to identify KIs investigated or approved for lung cancer treatment and associated with hyperlipidemia. In addition, the most recent clinical trials and atherosclerotic CVD guidelines for the general and cancer patient populations were also reviewed.</div></div><div><h3>Results</h3><div>Among KIs, ALK inhibitors, mammalian target of rapamycin inhibitors, Janus kinase inhibitors, and multikinase inhibitors demonstrated clinical benefits for patients with lung cancer but are also associated with hyperlipidemia. Optimal target levels for total cholesterol, low-density lipoprotein cholesterol, and triglycerides in managing KI-associated hyperlipidemia for the primary and secondary prevention of CVD were recommended. Furthermore, we proposed strategies that include baseline risk assessment, regular blood lipid monitoring, and timely pharmacological interventions. Dose adjustments and discontinuation, evaluation for drug-drug interactions, patient education, and lifestyle modifications were also detailed.</div></div><div><h3>Conclusions</h3><div>A multifaceted approach is proposed for lung cancer patients receiving KI therapy to manage hyperlipidemia, minimize CVD risks, optimize treatment outcomes, and improve quality of life.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"143 ","pages":"Article 103065"},"PeriodicalIF":10.5,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sequencing antibody–drug conjugates in metastatic breast cancer: A systematic review","authors":"Luiz F. Costa de Almeida ,&nbsp;Luís Felipe Leite ,&nbsp;Anelise Poluboiarinov Cappellaro ,&nbsp;Lucas Diniz da Conceição ,&nbsp;Mariana Macambira Noronha ,&nbsp;Jessé Lopes da Silva ,&nbsp;Andreia Cristina de Melo ,&nbsp;Felipe Batalini ,&nbsp;Paolo Tarantino","doi":"10.1016/j.ctrv.2025.103067","DOIUrl":"10.1016/j.ctrv.2025.103067","url":null,"abstract":"<div><h3>Background</h3><div>Antibody–drug conjugates (ADCs) have redefined the treatment landscape of metastatic breast cancer (mBC), offering durable responses across all subtypes. As multiple ADCs with similar payloads become available for the same patient over the course of the disease, determining the optimal sequencing strategy has become an urgent need, particularly given concerns about cross-resistance and reduced efficacy.</div></div><div><h3>Methods</h3><div>A literature search identified 1868 citations, of which 23 studies (n = 2934 patients) met the inclusion criteria, encompassing ten full-text publications and 13 abstracts. Data on clinical subtypes, sequencing strategies, efficacy outcomes, and real-world evidence (RWE) were extracted and analyzed.</div></div><div><h3>Results</h3><div>In HER2-low mBC, initial ADC exposure produced higher response rates and longer PFS than subsequent ADCs, with median PFS declining from 5.1–7.6 months to 2.1–3.1 months and OS from 16.5–22.8 months to 5.6–8.0 months. In HER2-positive disease, clinical activity was partially preserved with the second ADC, particularly when T-DXd followed T-DM1, with sustained PFS. TNBC and HR+/HER2– cohorts showed a consistent decline in efficacy with second ADC exposure (PFS 2.5–3.1 months). Evidence indicates that switching ADC payloads mitigates cross-resistance, with improved ORR and PFS2 compared to same-payload sequences. Bridging chemotherapy between ADCs did not compromise efficacy and, in some cohorts, yielded a longer PFS than direct sequencing with another ADC with the same payload.</div></div><div><h3>Conclusion</h3><div>Emerging evidence indicates that sequential ADC use can be effective despite some cross-resistance, especially when distinct payload mechanisms are employed. Clinical use should consider payload type, timing, and breast cancer subtype, but toxicities remain critical for decision-making. Research providing insights into resistance mechanisms and biomarkers is needed for personalized approaches.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"142 ","pages":"Article 103067"},"PeriodicalIF":10.5,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical performance of tumor-informed versus tumor-agnostic ctDNA assays for colorectal cancer recurrence: A systematic review and diagnostic accuracy meta-analysis","authors":"Daniel G. Camblor ,&nbsp;Belén Martínez-Castedo ,&nbsp;Jorge Martín-Arana ,&nbsp;Francisco Gimeno-Valiente ,&nbsp;Blanca García-Micó ,&nbsp;Francisco Martínez-Picó ,&nbsp;Víctor Seguí ,&nbsp;Miguel García-Bartolomé ,&nbsp;Diego González ,&nbsp;Alejandro Guimera ,&nbsp;Marisol Huerta ,&nbsp;Susana Roselló ,&nbsp;Valentina Gambardella ,&nbsp;Desamparados Roda ,&nbsp;Leontios Pappas ,&nbsp;Aparna Parikh ,&nbsp;Juan Antonio Carbonell-Asins ,&nbsp;Andrés Cervantes ,&nbsp;Noelia Tarazona","doi":"10.1016/j.ctrv.2025.103066","DOIUrl":"10.1016/j.ctrv.2025.103066","url":null,"abstract":"<div><div>In patients with early-stage colorectal cancer (CRC), circulating tumor DNA (ctDNA) testing is increasingly used to detect minimal residual disease (MRD) after curative-intent surgery. This information can guide decisions on adjuvant chemotherapy and surveillance. Two main approaches exist, tumor-informed (TI) and tumor-agnostic (TA), however, their diagnostic accuracy in clinical practice remains unclear. We conducted a bivariate diagnostic meta-analysis to compare sensitivity and specificity of TI versus TA ctDNA assays for detecting recurrence in patients with resected CRC. Subgroup analyses were performed based on landmark versus serial sampling strategies. In the serial-sampling setting, TI assays demonstrated markedly higher sensitivity than TA assays (0.88 vs. 0.59; p = 0.001), with no significant differences in false-positive rates. The landmark analyses did not show statistically significant differences between approaches. The results underscore the importance of sampling strategy when selecting a ctDNA test. When longitudinal monitoring is feasible, TI assays provide the most reliable detection of recurrence. This meta-analysis supports tailoring ctDNA testing to the clinical context, prioritizing TI approaches for serial surveillance to better guide adjuvant decision-making and improve patient outcomes.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"142 ","pages":"Article 103066"},"PeriodicalIF":10.5,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renal adverse events associated with cyclin-dependent kinase 4/6 inhibitors","authors":"Hassan Izzedine ,&nbsp;Rimda Wanchoo ,&nbsp;Ruby Sharma ,&nbsp;Kenar D. Jhaveri","doi":"10.1016/j.ctrv.2025.103060","DOIUrl":"10.1016/j.ctrv.2025.103060","url":null,"abstract":"<div><div>Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (CDK4/6i) have emerged as a standard of care for hormone receptor-positive (HR + ), human epidermal growth factor receptor 2-negative (HER2-) breast cancer, significantly improving patient survival. While generally well-tolerated, their use is associated with a spectrum of adverse events, particularly impacting renal, cardiovascular, and metabolic systems. Clinical data indicate a higher incidence of nephrotoxic adverse reactions in patients receiving CDK4/6i compared to control groups, with abemaciclib showing the highest risk ratio. These renal effects can manifest as true acute kidney injury (AKI), including rare cases of acute tubular injury and acute interstitial nephritis, or as a more common “pseudo-AKI.” The latter is characterized by an increase in serum creatinine due to the inhibition of renal organic cation transporters (OCT2/MATE), often without an actual decline in glomerular filtration rate (GFR). This highlights the importance of utilizing cystatin C alongside creatinine for accurate GFR assessment. Preclinical studies suggest a complex effect on renal health; while some data indicate acute nephroprotection, long-term rodent models treated with palbociclib after ischemic AKI demonstrated impaired recovery, increased renal fibrosis, and cellular senescence, indicating potentially detrimental long-term chronic effects. Beyond renal considerations, CDK4/6i are also associated with hypertension and electrolyte imbalance like hypokalemia and hyponatremia. Furthermore, these agents are susceptible to significant drug-drug interactions, particularly with CYP3A4 inhibitors/inducers and immunosuppressants, necessitating careful dose adjustments and monitoring, especially in solid organ transplant recipients. This review consolidates current evidence regarding the renal of CDK4/6i, emphasizing the need for vigilant monitoring and a multidisciplinary approach to optimize patient outcomes.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"142 ","pages":"Article 103060"},"PeriodicalIF":10.5,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endocrine-based strategies after CDK4/6 inhibitors in biomarker-selected subgroup of hormone receptor positive advanced breast cancer: A systematic review and network meta-analysis","authors":"Alicia Escudero ,&nbsp;Meritxell Bellet ,&nbsp;Cristina Saura ,&nbsp;Anna Aguilera ,&nbsp;Andri Papakonstantinou ,&nbsp;Pablo Tolosa ,&nbsp;José Ángel García-Sáenz ,&nbsp;Fernando Moreno ,&nbsp;Alfonso López de Sá ,&nbsp;Francesco Schettini ,&nbsp;Elia Seguí ,&nbsp;Marta Gonzalez-Rodriguez ,&nbsp;Victor Navarro ,&nbsp;Juan Manuel Ferrero-Cafiero ,&nbsp;Xavier González ,&nbsp;Cristina Hernando ,&nbsp;Alexios Matikas ,&nbsp;Aleix Prat ,&nbsp;Mafalda Oliveira ,&nbsp;Tomas Pascual ,&nbsp;Guillermo Villacampa","doi":"10.1016/j.ctrv.2025.103063","DOIUrl":"10.1016/j.ctrv.2025.103063","url":null,"abstract":"<div><h3>Background</h3><div>Several endocrine-based strategies have been evaluated following CDK4/6 inhibition (CDK4/6i) in hormone receptor–positive advanced breast cancer. However, the absence of head-to-head comparisons leave uncertainty regarding the optimal treatment selection.</div></div><div><h3>Methods</h3><div>A systematic literature search was performed to identify randomized controlled trials (RCTs) evaluating endocrine-based strategies after CDK4/6i for hormone receptor-positive advanced breast cancer. A network <em>meta</em>-analysis was used to compare overall treatment strategies, rather than individual treatments. In addition, an extracted individual patient data <em>meta</em>-analysis was conducted. The primary endpoint was progression-free survival (PFS) evaluated independently in tumors with PI3K-AKT-PTEN alterations, <em>ESR1</em>-mutated and wild-type tumors.</div></div><div><h3>Results</h3><div>A total of 20 RCTs including 4,716 patients were included. In <em>ESR1</em>-mutated tumors, oral SERD/SERM/PROTAC showed numerically better PFS compared with switching CDK4/6i plus fulvestrant (HR = 0.67, 95 % CI 0.45–1.00). In this population, the addition of i) CDK4/6i or ii) mTORi to oral SERDs improved PFS compared with oral SERD/SERM/PROTAC alone (HR = 0.44, 95 % CI 0.27–0.72 and HR = 0.45, 95 % CI 0.23–0.89, respectively). In PI3K-AKT-PTEN altered tumors, the greatest benefit was observed with PI3K/AKT/mTORi plus fulvestrant and oral SERDs plus CDK4/6i (P-scores &gt; 0.75). In <em>ESR1</em> and PI3K/AKT/PTEN wild-type tumors, several treatment combinations outperformed fulvestrant. The use of PI3K/AKT/mTORi plus fulvestrant was associated with the highest incidence of grade ≥ 3 adverse events (66.0 %).</div></div><div><h3>Conclusion</h3><div>This <em>meta</em>-analysis reinforces the importance of molecular stratification in treatment decisions after CDK4/6i progression, highlighting the need for efficacy and safety assessments across biomarker-selected subgroups.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"142 ","pages":"Article 103063"},"PeriodicalIF":10.5,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing epigenetics: Genome-wide DNA methylation assay for colorectal cancer therapy","authors":"Chikashi Ishioka","doi":"10.1016/j.ctrv.2025.103062","DOIUrl":"10.1016/j.ctrv.2025.103062","url":null,"abstract":"<div><div>Despite dramatic advances in cancer genomic medicine over the past decade, the complex and diverse nature of cancer makes it difficult to identify biomarkers for predicting treatment and prognosis in personalized medicine. The epigenome is a universal system that regulates genomic information and its expression and is involved in the development and progression of cancer. DNA methylation is a key epigenetic modification in cancer, leading to the inactivation of tumor suppressors and the activation of oncogenes through aberrant gene expression patterns. Therefore, epigenomic information may contain robust cancer biomarkers, suggesting that the development of epigenetic diagnostics will enable accurate disease stratification, prediction of treatment response and prognosis. However, in managing advanced colorectal cancer, as in other cancers, gene mutations and the expression of their products, but not epigenomic information, have been used to guide treatment or predict prognosis. This review explores the significance of DNA methylation in advanced colorectal cancer, focusing on its role in carcinogenesis and as a biomarker for predicting the efficacy of anti-EGFR antibody and prognosis. It also reviews the clinical application of recently developed genome-wide DNA methylation diagnostics and predicts the future of epigenomic diagnostics in cancer treatment.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"143 ","pages":"Article 103062"},"PeriodicalIF":10.5,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “The importance of education and training in neuroendocrine neoplasms: challenges and opportunities for multidisciplinary management”. [Cancer Treat. Rev. 139 (2025) 102998]","authors":"Francesco Panzuto ,&nbsp;Simona Barbi ,&nbsp;Annalisa Trama ,&nbsp;Nicola Fazio","doi":"10.1016/j.ctrv.2025.103043","DOIUrl":"10.1016/j.ctrv.2025.103043","url":null,"abstract":"","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"141 ","pages":"Article 103043"},"PeriodicalIF":10.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145427241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular senescence: A novel mechanism of therapeutic resistance in prostate cancer","authors":"Claire Lin ,&nbsp;Matthew J. Hadfield ,&nbsp;Amol Rathore ,&nbsp;Maximilian Pinho-Schwermann ,&nbsp;Shengliang Zhang ,&nbsp;Shaolei Lu ,&nbsp;Petra den Hollander ,&nbsp;Sendurai A. Mani ,&nbsp;Attila A. Seyhan ,&nbsp;Ariana Santopietro ,&nbsp;Anthony Mega ,&nbsp;Liang Cheng ,&nbsp;Wafik S. El-Deiry ,&nbsp;Benedito A. Carneiro","doi":"10.1016/j.ctrv.2025.103061","DOIUrl":"10.1016/j.ctrv.2025.103061","url":null,"abstract":"<div><div>Prostate cancer (PCa) is a leading cause of cancer-related morbidity and mortality. Despite the efficacy of androgen deprivation therapy (ADT), patients with advanced PCa eventually progress to a lethal castration-resistant disease state. Cellular senescence represents a stable growth arrest induced by stress signaling cascades or cancer therapeutics, and escape from a senescent state may be implicated in the development of castration resistance. We discuss the mechanisms promoting cellular senescence in PCa and its contribution to therapeutic resistance to ADT, PARP inhibitors, chemotherapy, and radiation. We also summarize the potential of senolytic and senomorphic therapies in targeting senescent prostate cancer cells in the setting of therapy-induced senescence.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"142 ","pages":"Article 103061"},"PeriodicalIF":10.5,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145662886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone metastases in NSCLC: Modern paradigms in management and supportive care","authors":"Gabriele Minuti ,&nbsp;Giorgia Pasqualini ,&nbsp;Alice Avancini ,&nbsp;Niccolò Giaj-Levra ,&nbsp;Francesca Colonese ,&nbsp;Alessandro Di Federico ,&nbsp;Alessandra Fozza ,&nbsp;Michele Montrone ,&nbsp;Emanuela Olmetto ,&nbsp;Edoardo Pastorello ,&nbsp;Maria Lucia Reale ,&nbsp;Silvia Teresa Riva ,&nbsp;Elisa Roca ,&nbsp;Claudio Sini ,&nbsp;Giuseppe Viscardi ,&nbsp;Sara Pilotto ,&nbsp;Francesco Passiglia","doi":"10.1016/j.ctrv.2025.103051","DOIUrl":"10.1016/j.ctrv.2025.103051","url":null,"abstract":"<div><div>Bone metastases (BoMs) are a frequent complication in advanced non-small-cell lung cancer (NSCLC), affecting approximately one third of patients at diagnosis and 35–60 % during the disease course. BoMs increase the risk of skeletal-related events (SREs), which have a detrimental impact on prognosis, performance status, and quality of life (QoL). Management of BoMs in NSCLC requires a multimodal approach. Although systemic anti-cancer therapies remain the cornerstone, the optimal management of BoMs in NSCLC also encompasses bone-targeted agents (BTAs) such as bisphosphonates and denosumab, local treatments including radiotherapy and surgical interventions, and supportive care strategies aimed at preventing SREs, alleviating pain, preserving mobility, and maintaining QoL. This review provides an updated overview of best practices for managing BoMs in NSCLC, covering diagnostic work‑up, therapeutic strategies, and the growing role of multidisciplinary care. It emphasizes the importance of supportive interventions, including nutrition and physical activity, to optimize outcomes in the era of targeted and immune-based therapies, alongside comprehensive simultaneous care.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"142 ","pages":"Article 103051"},"PeriodicalIF":10.5,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145571125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical overview of trophoblast surface antigen 2 antibody-drug conjugates in non–small cell lung cancer","authors":"Sandip Pravin Patel ,&nbsp;Shirish Gadgeel ,&nbsp;Mari Mino-Kenudson ,&nbsp;Jarushka Naidoo ,&nbsp;Nan Sethakorn","doi":"10.1016/j.ctrv.2025.103050","DOIUrl":"10.1016/j.ctrv.2025.103050","url":null,"abstract":"<div><div>Lung cancer remains the leading cause of cancer-related death in the United States, with non–small cell lung cancer (NSCLC) accounting for most lung cancer cases. Improvements in first-line treatment with immuno-oncology and targeted therapies have been observed in patients with NSCLC, but benefits may be limited for those with advanced or metastatic NSCLC (mNSCLC). Following progression on frontline therapies, later-line therapies offer modest benefits and are associated with pronounced adverse effects. Accordingly, there is a need for new, more effective options to improve survival and quality of life. Trophoblast surface antigen 2 (TROP2) antibody-drug conjugates (ADCs) are a novel approach to address unmet treatment needs in NSCLC. There are 5 TROP2-directed ADCs currently under investigation for treatment of NSCLC: datopotamab deruxtecan, sacituzumab govitecan, sacituzumab tirumotecan, DB-1305, and SHR-A1921. Here, we provide an overview of the properties of each ADC as well as efficacy and safety data from clinical trials of patients with NSCLC with or without actionable genomic alterations (AGAs). The unique characteristics of each ADC and its components, particularly the linker chemistry and payload attributes, define the mechanism of action and subsequently influence dosing, efficacy, and safety. TROP2 ADCs have shown antitumor responses with a manageable safety profile in patients with mNSCLC in several ongoing and completed trials. Additional studies are required to understand how these agents can be effectively integrated into the treatment paradigm for lung cancer, taking into consideration sequential use of multiple ADCs, resistance mechanisms, combination therapies, and use in special populations.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"143 ","pages":"Article 103050"},"PeriodicalIF":10.5,"publicationDate":"2025-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}