Cancer treatment reviews最新文献

{"title":"Combining antibody-drug conjugates with immune checkpoint inhibitors: A new paradigm for breast cancer therapy","authors":"Xiaoxiao Xu ,&nbsp;Tong Yu ,&nbsp;Zhenxing Wang","doi":"10.1016/j.ctrv.2025.103012","DOIUrl":"10.1016/j.ctrv.2025.103012","url":null,"abstract":"<div><div>The use of antibody-drug conjugates (ADCs) and immune checkpoint inhibitors (ICIs) has revolutionized the treatment of breast cancer. ADCs deliver cytotoxic payloads to tumor cells via antigen-targeted monoclonal antibodies, triggering direct cytotoxicity and immunomodulatory effects such as immunogenic cell death (ICD), antibody-dependent cellular cytotoxicity (ADCC), and dendritic cell activation. Preclinical and clinical studies highlight the synergistic effect of combining ADCs with ICIs: ADCs enhance tumor immunogenicity by releasing neoantigens, while ICIs reinvigorate T-cell-mediated antitumor responses by blocking the PD-1/PD-L1 or CTLA-4 pathways. This review explores the synergistic potential of combining ADCs and ICIs in the treatment of breast cancer, with an emphasis on mechanistic synergy and clinical outcomes. Notably, overlapping toxicities require careful monitoring. Additionally, novel immune checkpoint-targeted drug conjugates (IDCs) exhibit potential through dual-targeting and immunomodulatory mechanisms. Future efforts should focus on optimizing patient selection and developing next-generation conjugates to maximize efficacy while minimizing adverse effects.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"140 ","pages":"Article 103012"},"PeriodicalIF":10.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144831066","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":"Emerging mechanisms of triple-negative breast cancer radioresistance: Interplay between cancer cell mechanisms and the tumor immune microenvironment","authors":"Ana Canha-Borges ,&nbsp;Bárbara Nunes ,&nbsp;Sofia Torres Quintas ,&nbsp;Joana Paredes ,&nbsp;Lydia Meziani ,&nbsp;Michele Mondini ,&nbsp;Maria José Oliveira ,&nbsp;Eric Deutsch ,&nbsp;Flávia Castro","doi":"10.1016/j.ctrv.2025.103026","DOIUrl":"10.1016/j.ctrv.2025.103026","url":null,"abstract":"<div><div>Breast cancer is the most common and deadliest cancer in women worldwide. Among the distinct subtypes<strong>,</strong> triple negative breast cancer (TNBC) stands out as the most aggressive one, showing high resistance to treatments, including chemotherapy, radiotherapy, and immunotherapy.</div><div>Radiotherapy remains a standard treatment for TNBC, offering significant benefits in reducing local relapse. However, resistance to radiotherapy remains a major challenge, limiting its effectiveness and narrowing treatment options. Radioresistance in TNBC is driven by both tumor cell-intrinsic mechanisms and tumor immune microenvironment (TIME)-related processes. Intrinsically, TNBC cells employ strategies such as enhanced DNA damage repair mechanisms, tumor hypoxia adaptation, activation of survival pathways, and the contribution of cancer stem cells and extracellular vesicles. Extrinsically, the TIME can further fuel resistance by recruiting immunosuppressive cells (myeloid-derived suppressor cells, macrophages, neutrophils and regulatory T cells) and by releasing factors that impair the antitumor immune response mediated by T cells and natural killer cells.</div><div>This review explores the dual contribution of cancer cell-specific mechanisms and TIME dynamics in TNBC radioresistance. We further discuss the paradoxical role of the immune system in radioresponse, highlighting emerging combination therapies, and address the challenges of translating these strategies into clinical applications. Ongoing clinical trials targeting radioresistance are also summarized, reflecting the latest efforts to enhance therapeutic outcomes for TNBC patients.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"140 ","pages":"Article 103026"},"PeriodicalIF":10.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216555","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":"Advances in the management of locally advanced rectal cancer: A shift toward a patient-centred approach to balance outcomes and quality of life","authors":"Marco Airoldi ,&nbsp;Susana Roselló ,&nbsp;Noelia Tarazona ,&nbsp;Marisol Huerta ,&nbsp;Leticia Pérez-Santiago ,&nbsp;Tania Fleitas ,&nbsp;Vicente Pla-Martí ,&nbsp;Alberto Puccini ,&nbsp;Desamparados Roda ,&nbsp;Andrés Cervantes","doi":"10.1016/j.ctrv.2025.103015","DOIUrl":"10.1016/j.ctrv.2025.103015","url":null,"abstract":"<div><div>The treatment of locally advanced rectal cancer (LARC) has undergone a significant evolution in recent years, shifting toward more selective strategies that balance oncological outcomes with quality of life (QoL) preservation. Total neoadjuvant treatment (TNT) has improved local control and reduced distant metastases, but its long-term toxicities have sparked growing interest in treatment de-escalation strategies aimed at minimizing adverse effects while maintaining efficacy. This review focuses on the therapeutic advancements for LARC, analysing both established standards and emerging innovations. We discuss the increasing adoption of organ-preserving approaches, particularly the Watch-and-Wait (WW) strategy for patients achieving a clinical complete response (cCR), and potentially the selective omission of radiotherapy in well-defined cases. Additionally, we explore and examine less invasive surgical techniques that preserve function without compromising cure rates. Beyond standard treatment approaches, we highlight the role of immunotherapy, particularly its breakthrough efficacy in LARC with deficient mismatch repair/microsatellite instability (dMMR/MSI), leading to the concept of immune-ablation: achieving complete tumor regression while sparing patients from chemotherapy, radiotherapy, and surgery. Ongoing research is investigating immunotherapy’s potential role also in proficient mismatch repair/microsatellite stable (pMMR/MSS) LARC. Finally, we discuss emerging predictive biomarkers, such as circulating tumor DNA (ctDNA) and radiomics, which might refine patient selection and guide treatment individualization. The future of LARC management lies in a precision-driven approach, where survival is optimized without compromising QoL. By embracing innovation and personalizing care, we are entering a new era where cure remains paramount, but never at the expense of the patient’s well-being.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"140 ","pages":"Article 103015"},"PeriodicalIF":10.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144893040","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":"Circulating tumor DNA as prognostic marker in patients with metastatic colorectal cancer undergoing systemic therapy: A systematic review and meta-analysis","authors":"Anja Holz ,&nbsp;Bidisha Paul ,&nbsp;Antonia Zapf ,&nbsp;Klaus Pantel ,&nbsp;Simon A. Joosse","doi":"10.1016/j.ctrv.2025.102999","DOIUrl":"10.1016/j.ctrv.2025.102999","url":null,"abstract":"<div><h3>Background</h3><div>The response to systemic therapy against metastatic colorectal cancer (mCRC) is currently assessed by radiologic imaging. However, an increasing number of studies have shown that circulating tumor DNA (ctDNA) as liquid biopsy can be used as an alternative method to assess therapy efficacy. We conducted a systematic review with subsequent meta-analysis of primary studies to assess the prognostic value of sequential liquid biopsies in patients with metastatic colorectal cancer treated with systemic therapy.</div></div><div><h3>Methods</h3><div>Randomized, non-randomized, and prospective observational studies, reporting on the change in ctDNA concentration in total cell-free DNA over the course of systemic therapy of patients treated for metastatic colorectal cancer to predict treatment response according to RECIST criteria were included.</div></div><div><h3>Results</h3><div>Fifty-six studies involving 3735 evaluable patients with metastatic colorectal cancer were included in the meta-analysis. ctDNA increase during systemic therapy as compared to baseline was strongly associated with progression-free survival (HR: 2.44, 95% CI: 2.02–2.95) and overall survival (HR: 2.53, 95% CI: 2.01–3.18), which were reported in 39 and 33 studies, respectively.</div></div><div><h3>Conclusion</h3><div>Our analyses underscore the strong prognostic value of longitudinal plasma-based ctDNA analysis through liquid biopsy in mCRC patients. Subsequent research should evaluate the role of ctDNA in guiding therapy decisions, particularly in identifying patients likely to benefit from continuation or change of systemic therapy. While further standardization of ctDNA testing remains necessary, current evidence supports integrating serial ctDNA monitoring into upcoming clinical mCRC intervention trials, to lay the groundwork for its inclusion into future RECIST versions.</div></div><div><h3>Protocol registration</h3><div>The protocol for this review was registered on PROSPERO (CRD42023420012).</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"139 ","pages":"Article 102999"},"PeriodicalIF":10.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724589","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":"Palliative systemic therapy for locally advanced or metastatic salivary duct carcinoma: A comprehensive review","authors":"Masafumi Kanno ,&nbsp;Satoshi Kano ,&nbsp;Yoshinori Imamura ,&nbsp;Daisuke Kawakita ,&nbsp;Norihiko Narita ,&nbsp;Yuichiro Tada ,&nbsp;Yumi Ito ,&nbsp;Taiyo Morikawa ,&nbsp;Yoshimasa Imoto ,&nbsp;Yukinori Kato ,&nbsp;Tetsuji Takabayashi ,&nbsp;Shigeharu Fujieda","doi":"10.1016/j.ctrv.2025.102993","DOIUrl":"10.1016/j.ctrv.2025.102993","url":null,"abstract":"<div><div>Salivary duct carcinoma (SDC) is a rare and highly aggressive malignancy of the salivary glands. For patients ineligible for curative surgery or definitive radiotherapy, treatment options remain limited owing to the absence of standardized therapeutic protocols. This review draws upon major salivary gland cancer guidelines and integrates molecular profiles with clinical response data to propose an evidence-based treatment algorithm that stratifies patients into four groups according to the expression status of human epidermal growth factor receptor 2 (HER2) and androgen receptor (AR).</div><div>In HER2-positive tumors, HER2-targeted therapy constitutes the standard of care, with trastuzumab plus docetaxel providing clinical benefit. Antibody-drug conjugates, such as trastuzumab deruxtecan, have demonstrated efficacy even in patients with disease progression during trastuzumab-based therapy. In AR-positive tumors, androgen deprivation therapy, particularly combined androgen blockade, has demonstrated clinical activity, though concurrent molecular characteristics may influence treatment outcomes.</div><div>In HER2-positive/AR-positive tumors, HER2-targeted therapy is generally prioritized, although the absence of validated predictive biomarkers and defined thresholds remains a clinical challenge. For HER2-negative and AR-negative tumors, or those refractory to either or both targeted approaches, cytotoxic chemotherapy remains a viable option. Immune checkpoint inhibitors may offer benefits in tumors with high PD-L1 expression, although data on their role in SDC remain limited. Next-generation sequencing is recommended to identify actionable alterations (e.g., <em>NTRK</em>, <em>BRAF</em>, <em>FGFR</em>, <em>HRAS</em>) that may guide targeted therapy or clinical trial enrollment. Integrating comprehensive molecular profiling into treatment decision-making is essential to optimizing outcomes in advanced SDC.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"139 ","pages":"Article 102993"},"PeriodicalIF":9.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655636","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":"Overcoming Resistance to CDK4/6 inhibitors in Hormone Receptor positive, HER2 negative breast cancer: Innovative Combinations and Emerging Strategies","authors":"Federica Giugliano ,&nbsp;Carmine De Angelis ,&nbsp;Barbara Pistilli ,&nbsp;Giulia Viale ,&nbsp;Giampaolo Bianchini ,&nbsp;Mario Giuliano ,&nbsp;Luca Malorni ,&nbsp;Beatrice Taurelli Salimbeni ,&nbsp;Angela Esposito ,&nbsp;Antonio Giordano ,&nbsp;Timothy A. Yap ,&nbsp;Giuseppe Curigliano ,&nbsp;Carmen Criscitiello","doi":"10.1016/j.ctrv.2025.102980","DOIUrl":"10.1016/j.ctrv.2025.102980","url":null,"abstract":"<div><div>Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) improve outcomes patients affected by metastatic and early-stage hormone receptor-positive, HER2-negative breast cancer. However, approximately 20% of these tumors exhibit intrinsic resistance to such therapies, and most develop acquired resistance mechanisms that drive progression. Biomarker analyses of biological samples from patients treated with CDK4/6i plus ET have identified potential targets for therapeutic combinations. In this review, we discuss the mechanisms of action and resistance to CDK4/6i, providing a comprehensive overview of emerging efficacy and safety data, biomarker-driven strategies, and ongoing clinical trials. Finally, we delineate key research priorities aimed at guiding the development of innovative therapeutic combinations.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"139 ","pages":"Article 102980"},"PeriodicalIF":9.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330688","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":"The importance of education and training in neuroendocrine neoplasms: challenges and opportunities for multidisciplinary management","authors":"Francesco Panzuto ,&nbsp;Simona Barbi ,&nbsp;Annalisa Trama ,&nbsp;Nicola Fazio","doi":"10.1016/j.ctrv.2025.102998","DOIUrl":"10.1016/j.ctrv.2025.102998","url":null,"abstract":"<div><div>Neuroendocrine neoplasms (NENs) exemplify the challenges and opportunities inherent in managing rare cancers. Their rarity, biological heterogeneity, and diagnostic complexity necessitate a highly structured and multidisciplinary approach to patient care. In this context, education and training emerge as central pillars for improving clinical outcomes.</div><div>This review highlights how integrating multidisciplinary teams of diverse medical specialties enhances diagnostic accuracy, refines therapeutic strategies, and ensures adherence to evolving best practices. Establishing dedicated training pathways—both through traditional educational models and innovative digital platforms—is crucial to address the unique learning needs posed by NENs.</div><div>Scientific societies play a pivotal role by producing guidelines and fostering continuous professional development, although notable variability across international recommendations emphasizes the need for clinicians to harmonize and interpret critically. Patient advocacy groups, meanwhile, have become essential actors in the educational ecosystem, bridging informational gaps and advocating for patient-centered research and policy initiatives.</div><div>Emerging technologies, particularly artificial intelligence, offer promising tools to support clinical education and decision-making, provided that their implementation is cautious, validated, and integrated under healthcare professionals’ guidance.</div><div>By analyzing the NEN model, this review underscores that the future of rare cancer management relies on building strong collaborative networks, promoting standardized yet flexible educational programs, and embracing technological innovation, always focusing on quality, safety, and patient-centered care.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"139 ","pages":"Article 102998"},"PeriodicalIF":9.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703596","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":"A systematic review of phase I trials in patients with ovarian cancer","authors":"Giuliana Pavone ,&nbsp;Federica Martorana ,&nbsp;Vincenza Ricco ,&nbsp;Esteban Andres Ciliberti ,&nbsp;Marta Nerone ,&nbsp;Cristiana Sessa ,&nbsp;Ilaria Colombo","doi":"10.1016/j.ctrv.2025.102982","DOIUrl":"10.1016/j.ctrv.2025.102982","url":null,"abstract":"<div><h3>Background</h3><div>Ovarian cancer (OC) is the leading cause of death among gynecological malignancies, with limited treatment options for advanced and platinum-resistant disease. This systematic review analyzes phase I trials to assess recent therapeutic advancements.</div></div><div><h3>Methods</h3><div>We performed a systematic review of phase I trials in OC, published between 2012 and 2023, retrieving data on trial characteristics and outcomes. Studies were classified according to the tested treatment strategies into chemotherapy-only (CO), chemotherapy + non-chemotherapy agents (CNC) and chemotherapy-free (CF).</div></div><div><h3>Results</h3><div>78 trials were included, with more than 50 % of them published in the last four years. Overall, chemotherapy and immunotherapy were the most investigated agents. Fourteen trials (17.9 %) evaluated a CO strategy, 42 (53.8 %) a CNC combination and 22 (28.2 %) a CF therapy. Dose-limiting toxicities and toxic deaths were observed in 71 % and 100 % of CO studies, in 45.2 % and 21 % of CNC trials and in 37.4 % and 13.6 % of CF trials, respectively. CNC regimens outperformed the other treatment types in terms of efficacy outcomes, including overall response rate (11.5 % CO; 32.2 % CNC; 25.5 % CF), clinical benefit rate (40 % CO; 62 % CNC; 52 % CF) and median progression free survival (mPFS 5.9 months CO; 6.45 months CNC; 4.85 months CF). Trials enrolling platinum resistant or agnostic patients displayed worse clinical outcomes.</div></div><div><h3>Conclusions</h3><div>In the last years, there has been an increasing number of phase 1 trials assessing new agents and new combinations in patients with OC. Chemotherapy-free strategies display a more favorable safety profile, while regimens combining CNC agents seem to be more effective compared to CO approaches.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"139 ","pages":"Article 102982"},"PeriodicalIF":9.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144502652","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":"Tepotinib in patients with MET exon 14 skipping non-small cell lung cancer","authors":"Paul K. Paik ,&nbsp;Wade T. Iams ,&nbsp;Hatim Husain ,&nbsp;Richard M. O’Hara Jr ,&nbsp;Emmanuel Adewusi ,&nbsp;Xiuning Le","doi":"10.1016/j.ctrv.2025.102990","DOIUrl":"10.1016/j.ctrv.2025.102990","url":null,"abstract":"<div><div>The management of non-small cell lung cancer (NSCLC) has been transformed by the identification of specific therapies which target oncogenic drivers, including <em>MET</em> exon 14 (<em>MET</em>ex14) skipping, which occurs in 3–4% of patients. The development of selective MET inhibitors, such as tepotinib, has provided much-needed oral, targeted treatment options for these patients who otherwise have poor outcomes. In the largest trial involving patients with <em>MET</em>ex14 skipping NSCLC, the Phase II VISION study, tepotinib demonstrated robust and durable efficacy, which was especially notable when used in the first-line setting. Subgroup analyses demonstrated consistent efficacy in older and younger patients, Asian patients, and patients with brain metastases. The trial supported initial approval of tepotinib in Japan in 2020 and later in the US (accelerated approval: 2021; full approval: 2024) and many other countries worldwide. Here we delve into published literature on tepotinib, overview the mechanism of action and pharmacology, and provide a deep-dive into data from the pivotal VISION study, examining long-term outcomes, insights relevant for treatment sequencing, and biomarker analyses. We also discuss real-world data for tepotinib, indirect comparisons versus immuno- and/or chemotherapy, and provide experience from clinical practice, including guidance on managing adverse events, to provide a valuable aid for clinical practitioners.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"139 ","pages":"Article 102990"},"PeriodicalIF":10.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144722878","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":"Immunocytokines in cancer treatment: A systematic review","authors":"Stefano Agliardi ,&nbsp;Chiara Veronese ,&nbsp;Ferdinando Panzeri ,&nbsp;Simonetta Palazzini ,&nbsp;Greta Guarnieri ,&nbsp;Stefano Loiacono ,&nbsp;Vanessa Martinelli ,&nbsp;Anna Maria Potenza ,&nbsp;Emanuele Sbraga ,&nbsp;Eleonora Rissotto ,&nbsp;Elvira Inglese ,&nbsp;Federica Tosi ,&nbsp;Federica Villa ,&nbsp;Giorgio Patelli ,&nbsp;Letizia Monti ,&nbsp;Arianna Pani ,&nbsp;Romano Danesi ,&nbsp;Diego Fornasari ,&nbsp;Salvatore Siena ,&nbsp;Andrea Sartore-Bianchi","doi":"10.1016/j.ctrv.2025.102978","DOIUrl":"10.1016/j.ctrv.2025.102978","url":null,"abstract":"<div><h3>Introduction</h3><div>Immunocytokines are an emerging class of antibody-cytokine fusion proteins combining the specificity of monoclonal antibodies with the potent immunostimulatory effects of cytokines, potentially enhancing the anti-tumor immune response while reducing systemic toxicity.</div></div><div><h3>Methods</h3><div>We conducted a systematic review following the PRISMA guidelines<strong>.</strong> We performed a comprehensive literature search using PubMed and <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> databases. The search strategy included the terms “immunocytokine”, “cytokine”, “tumor”, and “cancer”. Filters were applied to retrieve only peer-reviewed articles and clinical trials.</div></div><div><h3>Results</h3><div>25 publications were retrieved: 15 were Phase I studies; 2 Phase I/II, and 8 Phase II. Regarding ongoing clinical trials, 62 studies were included: 30 were Phase I studies, 2 Phase III, and the remaining 30 were either Phase II (n = 13) or Phase I/II (n = 17). In 50/62 trials, the primary and co-primary outcomes included safety measures, such as adverse effects, dose-limiting toxicities, and maximum tolerated dose. In both studies from literature and ongoing clinical trials, the most common target was extra-domain B (EDB) of fibronectin, and the most investigated type of cancer was melanoma. While all published studies focused on solid tumors, several ongoing trials include hematologic malignancies.</div></div><div><h3>Conclusions</h3><div>Research interest in immunocytokines as a potential cancer treatment is increasing, although only limited data are currently available. Several trials, mainly in the early phase, are ongoing, paving the way for a possible broader clinical application of this class of immunotherapeutics.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"139 ","pages":"Article 102978"},"PeriodicalIF":9.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338813","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}