Cancer treatment reviews最新文献

{"title":"Long and short-term efficacy and safety comparison of nab-paclitaxel versus paclitaxel combined with trastuzumab and pertuzumab for neoadjuvant treatment of HER2-positive breast cancer: A systematic review and meta-analysis","authors":"Ye Yuan ,&nbsp;Xin Long ,&nbsp;Mengya Wei ,&nbsp;Li Chen ,&nbsp;Ji Zhang ,&nbsp;Xumei Liu","doi":"10.1016/j.ctrv.2025.102975","DOIUrl":"10.1016/j.ctrv.2025.102975","url":null,"abstract":"<div><h3>Introduction</h3><div>Direct comparisons between nab-paclitaxel and solvent-based taxanes are scarce, with inconsistent results from mostly retrospective studies. High-level evidence comparing their efficacy in HER2-positive breast cancer remains lacking. Our study represents the first systematic review and <em>meta</em>-analysis to directly compare the long-term and short-term efficacy and safety of nab-paclitaxel versus solvent-based paclitaxel in combination with trastuzumab and pertuzumab for neoadjuvant treatment of HER2-positive breast cancer.</div></div><div><h3>Methods</h3><div>We performed a comprehensive literature search in PubMed, Embase, the Cochrane Library, CNKI, Wan Fang, and VIP databases to identify relevant studies published up to February 10, 2025. The search focused on studies involving patients with HER2-positive breast cancer who had not undergone prior treatments for their condition. These studies compared neoadjuvant therapies using either nab-paclitaxel-based chemotherapy (Nab-p arm) or solvent-based paclitaxel-based chemotherapy (Sb-p arm), both combined with pertuzumab and trastuzumab. The primary outcomes measured were event-free survival, disease-free survival, overall survival, and total pathological complete response. Secondary outcomes included objective response rate and adverse events. The quality of evidence was assessed using the GRADE methodology.</div></div><div><h3>Results</h3><div>A total of six studies, including 3 RCTs, 1 prospective cohort study and 2 real-world studies, involving 1556 patients were included. The Nab-p arm demonstrated numerically more favorable EFS, DFS compared to the Sb-p arm. There was no significant difference in OS between the Nab-p arm and the Sb-p arm. The Nab-p arm showed significant improvements in pCR (RR: 1.18, 95 % CI: 1.08–1.29, <em>p</em> &lt; 0.001), pCR (with only RCTs) (RR: 1.13, 95 % CI: 1.03–1.24, <em>p =</em> 0.009), and ORR (RR: 1.30, 95 % CI: 1.07–1.57, <em>p</em> = 0.007) compared to the Sb-p arm. The Nab-p arm showed a lower grade III/IV diarrhea rate (RR: 0.59, 95 % CI: 0.42–0.83, <em>p</em> = 0.003), grade III/IV thrombocytopenia rate (RR: 0.46, 95 % CI: 0.24–0.89, <em>p</em> = 0.02), grade I/II allergic reactions rate (RR: 0.60, 95 % CI: 0.46–0.78, <em>p</em> &lt; 0.001) and grade III/IV allergic reactions rate (RR: 0.33, 95 % CI: 0.14–0.82, <em>p</em> = 0.02), compared to the Sb-p arm. The Nab-p arm showed a higher grade I/II neuropathy rate (RR: 1.21, 95 % CI: 1.12–1.30, <em>p</em> &lt; 0.001) and grade III/IV neuropathy rate (RR: 2.61, 95 % CI: 1.23–5.52, <em>p</em> = 0.001), compared to the Sb-p arm.The outcome of pCR had moderate-quality evidence and the outcome of pCR (with only RCTs) had high-quality evidence.</div></div><div><h3>Conclusions</h3><div>Nab-paclitaxel exhibits short-term efficacy advantages over paclitaxel, but no significant long-term benefits. The two regimens have different safety profile.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"138 ","pages":"Article 102975"},"PeriodicalIF":9.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144240440","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":"Medical management of pancreatic cancer: from personalization to broadening treatment strategies","authors":"Nelson Dusetti ,&nbsp;Jean Baptiste Bachet ,&nbsp;Brice Chanez ,&nbsp;Cindy Neuzillet ,&nbsp;Louis de Mestier ,&nbsp;Nicolas Williet ,&nbsp;Nicolas Frauhoffer ,&nbsp;Remy Nicolle ,&nbsp;Alice Boilève ,&nbsp;Anthony Turpin ,&nbsp;Raphaël Rodriguez ,&nbsp;Jérôme Cros ,&nbsp;Juan Iovanna ,&nbsp;Pascal Hammel","doi":"10.1016/j.ctrv.2025.102973","DOIUrl":"10.1016/j.ctrv.2025.102973","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is one of the most heterogeneous and deadly cancers. This review examines recently implemented strategies to integrate predictive tools and targeted therapies to improve treatments personalization and patient outcomes. Predictive transcriptomic signatures based on machine learning should optimize first-line chemotherapy selection, while organoid-based chemo-profiling could help late-line or non-standard treatments, particularly when transcriptomic signatures are unavailable to guide therapeutic decisions. Liquid biopsies enable real-time, non-invasive monitoring of tumour progression and resistance. Targeted therapies, even limited to a small subset of PDAC patients, exploit specific molecular vulnerabilities and several of those are under clinical evaluation to join PDAC armamentarium. Given PDAC’s biological complexity, a multimodal approach combining predictive tools, functional testing, and molecularly-guided therapies is required to progress. Implementing those strategies in routine practice, combined with technological and clinical advances should enhance the precision, accessibility, and effectiveness of personalized PDAC treatment, as well as expand therapeutic options with new targets.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"138 ","pages":"Article 102973"},"PeriodicalIF":9.6,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144196109","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":"Key decision factors in second-line therapy: Expert insights on HR+/HER2-metastatic breast cancer post-CDK4/6 inhibitor progression","authors":"Roberto Buonaiuto ,&nbsp;Andrea Botticelli ,&nbsp;Carmen Criscitiello ,&nbsp;Maria Vittoria Dieci ,&nbsp;Nicola Fusco ,&nbsp;Lorenzo Gerratana ,&nbsp;Matteo Lambertini ,&nbsp;Umberto Malapelle ,&nbsp;Luca Malorni ,&nbsp;Carmine De Angelis","doi":"10.1016/j.ctrv.2025.102972","DOIUrl":"10.1016/j.ctrv.2025.102972","url":null,"abstract":"<div><div>The progression of HR+/HER2- metastatic breast cancer after treatment with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) poses significant therapeutic challenges. Endocrine therapy (ET) remains a cornerstone of subsequent treatment, but its effectiveness depends on a nuanced understanding of clinical and genomic factors that drive therapy selection. For example, the duration of response to prior CDK4/6i therapy strongly predicts sensitivity to subsequent ET. Patients with prolonged responses to first-line therapy may benefit most from additional endocrine strategies, whereas those with rapid cancer progression often require alternative approaches. Clinical parameters such as disease burden, visceral involvement, and comorbidities also guide treatment decisions. Low-burden, indolent disease favors continued ET, whereas aggressive progression may necessitate the addition of targeted agents or a shift to chemotherapy. Genomic profiling via liquid or tissue biopsy should be integral to identifying actionable mutations and ensuring timely, individualized intervention. Molecular parameters, such as <em>ESR1</em> mutations and PI3K pathway alterations, can predict therapeutic response, thus guiding treatment selection. This review underscores the importance of a personalized, evidence-based approach to the selection of endocrine-based therapy post-CDK4/6i failure, leveraging clinical insights and molecular diagnostics to optimize patient outcomes.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"138 ","pages":"Article 102972"},"PeriodicalIF":9.6,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144185408","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":"FGFR2b protein overexpression: An emerging biomarker in gastric and gastroesophageal junction adenocarcinoma","authors":"Elizabeth C. Smyth ,&nbsp;Kyoung-Mee Kim ,&nbsp;Sun Young Rha ,&nbsp;Zev A. Wainberg ,&nbsp;Hayden Honeycutt ,&nbsp;Erica Sommermann ,&nbsp;Atsushi Ochiai","doi":"10.1016/j.ctrv.2025.102971","DOIUrl":"10.1016/j.ctrv.2025.102971","url":null,"abstract":"<div><div>Gastric and gastroesophageal junction cancer (G/GEJC) is a heterogeneous and complex disease characterized by histologic and molecular subtypes. Although a growing number of treatments have improved survival outcomes in the advanced setting, the greatest therapeutic benefits are observed among patient populations eligible for biomarker-directed therapies. Fibroblast growth factor receptor 2 isoform IIIb (FGFR2b) is an emerging biomarker under phase 3 clinical investigation for G/GEJC with the novel monoclonal antibody bemarituzumab. FGFR2b protein overexpression in gastric cancer, together with its function in various oncogenic signaling pathways, makes it an attractive target for precision medicine and thereby has gained clinical interest for its potential prognostic role in G/GEJC. Thus, to explore the potential role of FGFR2b, this narrative review summarizes the role and mechanism of FGFR2b in advanced G/GEJC, describes appropriate detection methodology for FGFR2b protein overexpression, and discusses future considerations for precision treatment in advanced G/GEJC with respect to FGFR2b protein overexpression and the emergence of other biomarkers.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"139 ","pages":"Article 102971"},"PeriodicalIF":9.6,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655634","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":"Ovarian escape in premenopausal breast cancer: Challenges and strategies for optimizing hormone suppression","authors":"Lan Luo ,&nbsp;Yonglin Zhang ,&nbsp;Li Zhang ,&nbsp;Senguo Yang ,&nbsp;Tian Zhou ,&nbsp;Ke Luo ,&nbsp;Shu Liu","doi":"10.1016/j.ctrv.2025.102970","DOIUrl":"10.1016/j.ctrv.2025.102970","url":null,"abstract":"<div><div>Ovarian function suppression (OFS) is extensively acknowledged for its efficacy and benefits in the management of breast cancer among premenopausal women. While gonadotropin-releasing hormone agonists (GnRHa) serve as the fundamental component of OFS, a subset of patients experience incomplete estrogen suppression, leading to potential treatment failure and adverse outcomes. This review systematically examines ovarian escape (OE) during GnRHa treatment in premenopausal women with hormone receptor-positive (HR+) breast cancer and explores potential risk factors along with the underlying mechanisms. Discrepancies in defining menopausal status and assay variability complicate OE diagnosis; however, early detection and intervention can mitigate the risk of treatment failure. Current guidelines lack standardized guidelines for hormone monitoring, underscoring the need for personalized strategies to optimize OFS efficacy and mitigate risks. Further research is warranted to elucidate OE mechanisms and refine therapeutic approaches. By proposing evidence-based management strategies, this work advances personalized OFS approaches tailored to high-risk populations.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"139 ","pages":"Article 102970"},"PeriodicalIF":9.6,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144321569","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":"Adjuvant therapy after resection of intraductal papillary mucinous neoplasm-derived pancreatic cancer: A systematic review and meta-analysis","authors":"Joseph R. Habib ,&nbsp;Asad Saulat Fatimi ,&nbsp;Omar Mahmud ,&nbsp;Ingmar F. Rompen ,&nbsp;Benedict Kinny-Köster ,&nbsp;Lois A. Daamen ,&nbsp;Jin He ,&nbsp;I. Quintus Molenaar ,&nbsp;Marco Del Chiaro ,&nbsp;Christopher L. Wolfgang ,&nbsp;Ammar A. Javed ,&nbsp;Marc G. Besselink ,&nbsp;for the PANC-PALS Consortium","doi":"10.1016/j.ctrv.2025.102969","DOIUrl":"10.1016/j.ctrv.2025.102969","url":null,"abstract":"<div><h3>Introduction</h3><div>The management of intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic cancer is extrapolated from pancreatic intraepithelial neoplasm (PanIN)-derived pancreatic cancer. However, these cancers are biologically and clinically distinct and evidence regarding the role of adjuvant therapy (AT) is unclear. The aim of this systematic review and meta-analysis was to consolidate current evidence regarding survival benefit of AT for IPMN-derived pancreatic cancer.</div></div><div><h3>Methods</h3><div>Systematic searches of the PubMed, Embase, Scopus, Web of Science, and Cochrane CENTRAL databases were performed from inception to February 2nd, 2025. Studies that reported survival analyses comparing AT versus surgery alone for resected IPMN-derived pancreatic cancer were included. Risk of bias was assessed using the Newcastle-Ottawa scale. Hazard ratios were pooled using generic inverse-variance random-effects models.</div></div><div><h3>Results</h3><div>A total of 26 studies were included in this review. All studies were observational and 16 had low risk of bias while 10 had high risk of bias. AT was not associated with an OS benefit on pooled multivariable analysis (HR: 0.78 [0.47, 1.28]) in the total population. In subgroups of patients with pathology node-positive (pN1 or pN2) disease, advanced T-stage and overall AJCC tumor stage, elevated CA19-9 (&gt;37 IU), and poor grade of differentiation, AT was associated with OS benefit.</div></div><div><h3>Conclusions</h3><div>Current data suggests that routine AT after resection of IPMN-derived pancreatic cancer is not associated with an OS benefit and may constitute overtreatment. However, patients with high-risk features such as large or high-grade tumors, nodal disease, and elevated CA19-9 may benefit from AT.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"138 ","pages":"Article 102969"},"PeriodicalIF":9.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144177905","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":"Induction chemotherapy followed by chemoradiotherapy for locally advanced cervical cancer: A systematic review and meta-analysis","authors":"Matheus de Oliveira Andrade ,&nbsp;Otavio de Carvalho Modaffar Al-Alam ,&nbsp;Henrique Jin Son Kim ,&nbsp;João Pedro Thimotheo Batista ,&nbsp;Débora Maciel Santana Dornellas ,&nbsp;Ricardo Lima Coelho ,&nbsp;Vitória Espíndola Leite Borges ,&nbsp;Mariana Carvalho Gouveia ,&nbsp;Mariana Scaranti ,&nbsp;Renata Colombo Bonadio ,&nbsp;Stephanie Gaillard ,&nbsp;Samantha Cabral Severino Costa","doi":"10.1016/j.ctrv.2025.102959","DOIUrl":"10.1016/j.ctrv.2025.102959","url":null,"abstract":"<div><h3>Background</h3><div>The addition of induction chemotherapy (ICT) prior to concomitant chemoradiotherapy (CCRT) in the treatment of locally advanced cervical cancer (LACC) is controversial, as trials have yielded conflicting results. This study aims to evaluate the role of ICT followed by CCRT in LACC.</div></div><div><h3>Methods</h3><div>We systematically searched PubMed, Embase and Cochrane for studies with patients diagnosed with LACC receiving ICT followed by CCRT. Studies that included surgery, definitive radiotherapy (without concurrent chemotherapy), or immunotherapy were excluded.</div></div><div><h3>Results</h3><div>Among 5,282 screened studies, 20 met the inclusion criteria, representing 1,543 patients treated with ICT. A <em>meta</em>-analysis of the five controlled studies exhibited high heterogeneity in progression-free survival (PFS) and overall survival (OS), driven by the CIRCE trial — a study employing a platinum–gemcitabine ICT regimen lasting &gt; 6 weeks. Sensitivity analysis excluding this trial demonstrated a significant improvement in PFS (HR 0.46; 95 % CI 0.31–0.69; p = 0.0002) and OS (HR 0.68; 95 % CI 0.47–0.99; p = 0.049) with the addition of ICT to CCRT, compared to CCRT alone. Meta-analysis of proportions revealed a 2-year OS of 84.1 % for studies utilizing platinum–paclitaxel compared to 72.2 % for platinum–gemcitabine (p-value for subgroup difference = 0.022). Studies with ICT duration of ≤ 6 weeks showed a 2-year OS of 84.8 % compared to 71.7 % for ICT duration &gt; 6 weeks (p = 0.003).</div></div><div><h3>Conclusion</h3><div>In patients with LACC, ICT + CCRT significantly improves PFS and OS compared to CCRT alone, provided that the ICT involves a platinum doublet with paclitaxel and is administered within ≤ 6 weeks.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"138 ","pages":"Article 102959"},"PeriodicalIF":9.6,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144107539","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":"Paving the path ForwARd: Advances and challenges in androgen receptor targeting in breast cancer","authors":"Nithya Sridhar ,&nbsp;Toshiaki Iwase ,&nbsp;Xuemei Xie ,&nbsp;Jangsoon Lee ,&nbsp;Senthil Damodaran ,&nbsp;Naoto T. Ueno","doi":"10.1016/j.ctrv.2025.102958","DOIUrl":"10.1016/j.ctrv.2025.102958","url":null,"abstract":"<div><div>The role of androgen receptors (AR) in breast cancer is crucial for preclinical and clinical research. While AR-targeted therapy is a standard treatment for prostate cancer, the application of this therapeutic strategy to breast cancer has not been established. Indeed, AR is expressed in around 60–90% of breast cancers, making it imperative that we learn more about its prognostic and predictive impacts and targeting potential in breast cancer. Over the past decade, AR-targeted therapies ─ including AR antagonists and selective AR modulators ─ have shown promise in breast cancer treatment. However, an incomplete understanding of AR’s role across breast cancer subtypes hinders clinical application. The lack of standardized AR expression thresholds further complicates patient selection, underscoring the urgent need for biomarker-driven strategies to optimize AR-targeted approaches in breast cancer. In this review, we provide an overview of a clinical perspective of AR in breast cancer by discussing AR biology, AR as a biomarker, and AR-targeted therapy development. We present our review with a particular emphasis on the distinct roles of AR in ER-positive (ER+) and ER-negative (ER-) breast cancer subtypes. Finally, the paper addresses the hurdles that have impeded the development of a robust clinical landscape for AR-targeted therapies and possible solutions for overcoming these challenges.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"138 ","pages":"Article 102958"},"PeriodicalIF":9.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138692","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":"Dealing with KRAS G12C inhibition in non-small cell lung cancer (NSCLC) – biology, clinical results and future directions","authors":"Ilaria Attili ,&nbsp;Carla Corvaja ,&nbsp;Pamela Trillo Aliaga ,&nbsp;Ester Del Signore ,&nbsp;Gianluca Spitaleri ,&nbsp;Antonio Passaro ,&nbsp;Filippo de Marinis","doi":"10.1016/j.ctrv.2025.102957","DOIUrl":"10.1016/j.ctrv.2025.102957","url":null,"abstract":"<div><div><em>KRAS G12C</em> mutation occurs in ∼ 14 % of non-small cell lung cancer (NSCLC) patients and has been historically deemed undruggable, with immune-checkpoint inhibitors (ICIs) and platinum-based chemotherapy (PBC) representing the standard-of-care in the advanced setting. First-in-class, covalent <em>KRAS G12C</em> OFF-inhibitors sotorasib and adagrasib have revolutionized the therapeutic landscape and recently entered clinical practice. However, limited efficacy alongside toxicity profiles strengthen the need to design novel molecules and to optimize therapeutic strategies to address and overcome intrinsic and acquired resistance mechanisms. Moreover, <em>KRAS G12C</em> frequently co-occurs with <em>STK11/KEAP1</em> mutations, that represent a negative prognostic factor, being associated with increased metastatic potential and reduced overall survival and poorer outcomes with ICIs. Furthermore, the high incidence of brain metastases is common in <em>KRAS G12C-</em>mutant NSCLC, and the efficacy of standard therapies and KRAS G12C inhibitors in treating or preventing central nervous system involvement is still suboptimal.</div><div>In this context, novel inhibitors, such as broad-spectrum inhibitors targeting the active GTP-bound ON-state, pan-RAS ON inhibitors and allele-selective tricomplex inhibitors, have showed promising early clinical activity although their clinical utility needs to be further elucidated. In addition, targeting upstream, downstream and parallel signaling pathways through combination strategies might enhance the activity of KRAS G12C inhibitors and eventually improve clinical outcomes in this subset of NSCLC patients. Several combinations are currently under clinical investigation and promising approaches include combinations of KRAS G12C inhibitors with ICIs, SOS1, SHP2 inhibitors and PBC. Notwithstanding the potential improved efficacy of combination strategies, tolerability remains a critical challenge that must be carefully assessed and managed.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"137 ","pages":"Article 102957"},"PeriodicalIF":9.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068752","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":"Drug-Drug interactions and special considerations in breast cancer patients treated with CDK4/6 inhibitors: A comprehensive review","authors":"Taha Koray Sahin ,&nbsp;Gozde Kavgaci ,&nbsp;Deniz Can Guven ,&nbsp;Sercan Aksoy","doi":"10.1016/j.ctrv.2025.102956","DOIUrl":"10.1016/j.ctrv.2025.102956","url":null,"abstract":"<div><div>Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have reshaped the treatment paradigm of hormone receptor positive (HR + )/HER2-negative breast cancer in both adjuvant and metastatic settings. However, their metabolism via the cytochrome P450 (CYP3A4) pathway poses a high risk of clinically relevant drug-drug interactions (DDIs), requiring vigilant therapeutic strategies. This review provides a comprehensive analysis of the pharmacokinetics, metabolism, and interaction profiles of palbociclib, ribociclib, and abemaciclib, emphasizing their differential DDI risks. Among these agents, ribociclib has been associated with a higher risk of QTc prolongation and CYP3A4-mediated interactions in some studies, whereas abemaciclib demonstrates a relatively favorable DDI profile. However, data remain limited and are largely derived from indirect comparisons or pharmacovigilance analyses. We further examine the clinical implications of drug-drug interactions with frequently co-prescribed agents, including proton pump inhibitors, antifungal medications, anticoagulants, and lipid-lowering therapies. Practical recommendations regarding drug selection, therapeutic drug monitoring, and dose adjustment are discussed with attention to the individual characteristics of each CDK4/6i. Dose modifications and monitoring in patients with renal or hepatic impairment are also discussed. Emerging pharmacogenomic data suggest that genetic polymorphisms in CYP3A4 and ABCG2 influence drug exposure and toxicity, reinforcing the need for personalized treatment approaches. As the use of CDK4/6i expands across different breast cancer settings, addressing DDIs through precision medicine strategies such as pharmacogenomic profiling, physiologically based pharmacokinetic modeling, and artificial intelligence-guided clinical support will be essential to personalize therapy and optimize safety.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"137 ","pages":"Article 102956"},"PeriodicalIF":9.6,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942801","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}