Cancer treatment reviews最新文献

{"title":"Exploring resistance to immune checkpoints inhibitors in mismatch repair-deficient or microsatellite-instable colorectal cancer","authors":"Clara Salva de Torres ,&nbsp;Evelyn Elias ,&nbsp;Caterina Vaghi ,&nbsp;Nadia Saoudi González ,&nbsp;Ariadna García ,&nbsp;Adriana Alcaraz ,&nbsp;Marta Rodríguez-Castells ,&nbsp;Iosune Baraibar ,&nbsp;Javier Ros ,&nbsp;Francesc Salvà ,&nbsp;Josep Tabernero ,&nbsp;Elena Élez ,&nbsp;Enrique Sanz-Garcia","doi":"10.1016/j.ctrv.2026.103089","DOIUrl":"10.1016/j.ctrv.2026.103089","url":null,"abstract":"<div><div>Colorectal cancer (CRC) with mismatch-repair deficiency (dMMR) or high microsatellite instability (MSI-H) represents a distinct molecular subtype highly sensitive to immune checkpoint inhibitors (ICIs). Landmark clinical trials have established ICIs as standard-of-care in this setting, demonstrating durable responses and improved survival. However, up to one-third of patients will exhibit primary or acquired resistance, highlighting the urgent need for predictive biomarkers and novel therapeutic strategies. This review summarizes the clinical evidence supporting ICIs in dMMR/MSI-H CRC, explores mechanisms of resistance—including intrinsic and extrinsic modulators—and evaluates the role of potential predictive biomarkers of response. Finally, we discuss innovative therapeutic approaches to overcome resistance, including combination strategies, DNA repair pathway inhibitors, immune-oncology drugs beyond checkpoint inhibitors and microbiome-targeted interventions. Together, these insights aim to refine patient selection, optimize therapeutic benefit, and guide the development of next-generation therapies for dMMR/MSI-H CRC.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"143 ","pages":"Article 103089"},"PeriodicalIF":10.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973678","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":"KELIM score: A marker of chemosensitivity in ovarian cancer","authors":"Federica Adele Ambrosino ,&nbsp;Carmela Pisano ,&nbsp;Marilena Di Napoli ,&nbsp;Jole Ventriglia ,&nbsp;Rosa Tambaro ,&nbsp;Sabrina Rossetti ,&nbsp;Anna Passarelli ,&nbsp;Ernesta Cavalcanti ,&nbsp;Rossella De Cecio ,&nbsp;Francesco Fiore ,&nbsp;Sergio Venanzio Setola ,&nbsp;Teresa Troiani ,&nbsp;Lorenzo Lobianco ,&nbsp;Erica Perri ,&nbsp;Mariarosaria Lamia ,&nbsp;Gabriele Calvanese ,&nbsp;Sandro Pignata ,&nbsp;Sabrina Chiara Cecere","doi":"10.1016/j.ctrv.2025.103071","DOIUrl":"10.1016/j.ctrv.2025.103071","url":null,"abstract":"<div><div>Ovarian cancer is the gynecological cancer with the worst prognosis and the highest mortality rate, primarily because 75% of patients are diagnosed with advanced FIGO stage III-IV disease. About 50% of patients are now treated with neoadjuvant chemotherapy followed by interval debulking surgery. In that context, there is a need for accurate predictors of tumor primary chemosensitivity, as it may impact the feasibility of subsequent interval debulking surgery. The cancer antigen 125 ELIMination rate constant K (KELIM) score, a modeled kinetic parameter, is a potential marker of tumor chemosensitivity in patients with ovarian cancer treated with adjuvant or neoadjuvant chemotherapy before interval debulking surgery. This review aims to provide a comprehensive overview of potential predictive factors for response to platinum therapy, focusing on the KELIM score, a marker increasingly used in clinical practice.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"143 ","pages":"Article 103071"},"PeriodicalIF":10.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839647","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":"Comparative efficacy and safety of novel oral selective estrogen receptor degraders in ER+/HER2– advanced breast cancer: An updated systematic review and meta-analysis of randomized controlled trials","authors":"Najwaa Kirmani ,&nbsp;Nathalia De León-Fernández ,&nbsp;Juan David Rodriguez-Parra ,&nbsp;Laura Ghanem ,&nbsp;Bezalel Hakkeem ,&nbsp;Clara Briceño-Morales ,&nbsp;Ximena Briceño-Morales","doi":"10.1016/j.ctrv.2026.103093","DOIUrl":"10.1016/j.ctrv.2026.103093","url":null,"abstract":"<div><h3>Background</h3><div>Endocrine therapy (ET) plus CDK4/6 inhibitors (CDK4/6i) remains first-line (1 L) standard for ER+/HER2– metastatic breast cancer (mBC). However, <em>ESR1</em> mutations lead to ET resistance and subsequent disease progression (PD). Limitations of intramuscular fulvestrant have led to the development of novel oral selective estrogen receptor degraders (SERDs). We aim to evaluate efficacy and safety of novel oral SERDs for ER+/HER2– mBC.</div></div><div><h3>Methods</h3><div>PubMed, Embase, and Cochrane were systematically searched for randomized controlled trials (RCTs) comparing oral SERDs with standard treatment. Primary outcomes were progression-free survival (PFS) overall and by subgroups (<em>ESR1</em> mutation, menopausal status, age, prior CDK4/6i use, visceral metastases), PFS comparing oral SERDs versus fulvestrant in <em>ESR1</em>-mutated patients, and grade ≥ 3 or discontinuation due to treatment-related adverse events (TRAEs). Hazard and risk ratios (HRs/RRs) were pooled using random-effects models (RStudio 2025.09.2 + 418).</div></div><div><h3>Results</h3><div>Eight RCTs (n = 3,978) were included. Overall, PFS did not differ significantly between groups (HR 0.80; 95 % CI 0.62–1.04; <em>p = 0.09</em>). Statistically significant PFS subgroups included: <em>ESR1</em> mutation (HR 0.57; 95 % CI 0.45–0.73; <em>p &lt; 0.01</em>); prior CDK4/6i use (HR 0.68; 95 % CI 0.49–0.95; <em>p = 0.03</em>); visceral metastases (HR 0.78; 95 % CI 0.63–0.97; <em>p = 0.03</em>); age &lt; 65 years (HR 0.75; 95 % CI 0.60–0.92; <em>p = 0.01</em>); and oral SERDs versus fulvestrant (HR 0.55; 95 % CI 0.46–0.66; <em>p &lt; 0.01</em>). Grade ≥ 3 TRAEs were higher with SERDs (RR 1.64; 95 % CI 1.07–2.50; <em>p = 0.03</em>), while treatment discontinuation was not significant.</div></div><div><h3>Conclusions</h3><div>Novel oral SERDs may represent a paradigm shift in managing PD after 1 L therapy, showing potential to improve PFS in selected patients.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"143 ","pages":"Article 103093"},"PeriodicalIF":10.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973594","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":"Intracranial activity of antibody-drug conjugates in advanced non-small cell lung cancer: What have we accomplished so far?","authors":"Seng Wee Cheo ,&nbsp;Molly S.C. Li ,&nbsp;Derek De-Rui Huang ,&nbsp;Stephanie P.L. Saw ,&nbsp;Lizza E.L. Hendriks ,&nbsp;Jordi Remon ,&nbsp;Jessica Menis ,&nbsp;Alfredo Addeo ,&nbsp;Pei Jye Voon","doi":"10.1016/j.ctrv.2025.103083","DOIUrl":"10.1016/j.ctrv.2025.103083","url":null,"abstract":"<div><div>Antibody-drug conjugates (ADCs) represent a rapidly evolving class of therapeutics in non-small cell lung cancer (NSCLC), offering targeted delivery of cytotoxic payloads to tumor cells while minimizing off-target toxicity. Although ADCs have demonstrated promising results in NSCLC, their efficacy in treating central nervous system (CNS) metastases has been uncertain due to concerns over blood–brain barrier (BBB) penetration and the lack of dedicated CNS-specific evaluations in clinical trials. However, emerging evidence challenges this paradigm. While earlier-generation ADCs such as T-DM1 exhibited limited CNS efficacy, newer ADCs employing optimized linkers and cytotoxins demonstrate more favorable efficacy and toxicity profiles. Selected agents, including trastuzumab deruxtecan, datopotamab deruxtecan and patritumab deruxtecan, have all shown intracranial responses in patients with advanced NSCLC with brain metastases (BM). Proposed mechanisms facilitating CNS activity include BBB disruption by BM, membrane-permeable and highly potent cytotoxic payloads, and bystander effects that enable tumor cell killing beyond the target antigen. Nevertheless, several limitations remain, including variability in trial designs, limited number of patients with untreated CNS disease, and a lack of CNS-specific endpoints. Given the high incidence of BM in NSCLC and their significant impact on patient outcomes, there is an urgent need to better understand the intracranial activity of ADCs and whether they can prevent the development of CNS metastases, especially as some of these ADCS are being tested in the curative-intent setting. This review synthesizes current evidence and highlights ongoing trials, with a focused examination of the evolving role of ADCs in the management of BM.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"143 ","pages":"Article 103083"},"PeriodicalIF":10.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145882443","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":"AMH as a marker for resumption of ovarian function after chemotherapy: an IPD meta-analysis and systematic review","authors":"Charissa van Zwol – Janssens ,&nbsp;Mandy van M. Rosmalen ,&nbsp;Joop S.E. Laven ,&nbsp;Kazem Nasserinejad ,&nbsp;Jenny A. Visser ,&nbsp;Richard A. Anderson ,&nbsp;Irit Ben-Aharon ,&nbsp;Thomas Freour ,&nbsp;Kathryn J. Ruddy ,&nbsp;H. Irene Su ,&nbsp;Yvonne V. Louwers ,&nbsp;Agnes Jager","doi":"10.1016/j.ctrv.2025.103068","DOIUrl":"10.1016/j.ctrv.2025.103068","url":null,"abstract":"<div><h3>Background</h3><div>In premenopausal women with breast cancer, chemotherapy often leads to amenorrhea that could be temporary or permanent. Anti-Müllerian hormone (AMH) is a potential biomarker predicting resumption of ovarian function, an outcome that aids in the decision making for endocrine therapy. This study aimed to determine the predictive value of pre-chemotherapy AMH levels for resumption of ovarian function.</div></div><div><h3>Methods</h3><div>We conducted a systematic review and individual patient data (IPD) meta-analysis. Online databases were searched using terms including: AMH, prediction, menses, menses recovery, amenorrhea, chemotherapy-related amenorrhea, anovulation, menopause, infertility, ovarian reserve, premenopausal, breast cancer, chemotherapy. The study protocol was registered with PROSPERO (CRD42021233966).</div></div><div><h3>Results</h3><div>The systematic review included 31 studies, with 26 contributing to the meta-analysis. Eleven studies provided IPD from 1,029 women. Ovarian function resumption rates varied from 24 % to 61 % depending on follow-up time. Pre-chemotherapy AMH was significantly higher in women whose ovarian function resumed, standardized mean difference 0.94 (95 % CI 0.65–1.22) and showed good predictive ability for resumption of ovarian function (AUC 0.79–0.83). However, the identified cut-off values for pre-chemotherapy AMH gave high false negative rates and differed a lot between studies which was much determined by follow-up time, age and used AMH assay.</div></div><div><h3>Conclusion</h3><div>Pre-chemotherapy AMH shows association with ovarian function resumption, but a clinically reliable cut-off across assays could not be established using individual patient data. Therefore, due to high inter-assay variability, AMH is not suitable for optimizing endocrine therapy in premenopausal breast cancer patients at this time. Standardizing AMH assays can help in further research into a cut-off value.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"142 ","pages":"Article 103068"},"PeriodicalIF":10.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145835417","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 tumour DNA in head and neck squamous-cell carcinomas: A literature review","authors":"Léo Ventelou ,&nbsp;Angeline Ginzac ,&nbsp;Marie-Céleste Ferreira ,&nbsp;Laurie Canetti ,&nbsp;Soline Philippe ,&nbsp;Céleste Pinard ,&nbsp;Xavier Durando ,&nbsp;Maureen Bernadach","doi":"10.1016/j.ctrv.2025.103070","DOIUrl":"10.1016/j.ctrv.2025.103070","url":null,"abstract":"<div><h3>Background</h3><div>In 60 % of cases, head and neck cancers (HNCs) are diagnosed at an advanced stage and therefore have a poor prognosis with survival rates of only 49 months. Circulating tumour DNA (ctDNA) has emerged as a minimally invasive biomarker able to improve early detection, assess minimal residual disease, monitor systemic treatment response and identify therapeutic targets. This literature review aims to critically synthesise evidence from the past decade on the clinical use of ctDNA in both HPV-related and HPV-unrelated HNCs.</div></div><div><h3>Patients and methods</h3><div>A literature review was performed using PubMed and Cochrane Library on March 11th 2024, updated on November 21st, 2025, using the keywords: “circulating tumour DNA”, “head and neck cancer”, “ctHPV-DNA associated with HNSCC”, “liquid biopsy and HNSCC”.</div></div><div><h3>Results</h3><div>After evaluation of 363 articles identified, 92 were included. ctDNA has been investigated for screening, diagnosis, prognostic stratification, treatment-response assessment, relapse detection and identification of therapeutic targets. However, performance varies considerably across studies due to methodological and biological heterogeneity.</div></div><div><h3>Conclusion</h3><div>ctDNA shows strong potential for response assessment and post-treatment monitoring, particularly in HPV-related disease. Nevertheless, its integration into clinical practice requires methodological standardisation and validation in larger prospective studies.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"142 ","pages":"Article 103070"},"PeriodicalIF":10.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822356","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 “T-cell engager toxicity in clinical phase trials; A systematic review and meta-analysis”. [Cancer Treat Rev. 139 (2025) 102991. doi: 10.1016/j.ctrv.2025.102991]","authors":"Zoulikha M. Zaïr ,&nbsp;Gemma Butterworth ,&nbsp;Mariam Shalaby ,&nbsp;Eduard Oštarijaš ,&nbsp;Fiona Thistlethwaite","doi":"10.1016/j.ctrv.2025.103052","DOIUrl":"10.1016/j.ctrv.2025.103052","url":null,"abstract":"","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"142 ","pages":"Article 103052"},"PeriodicalIF":10.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145643969","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":"Primary tumor and metastasis-directed treatment for oligometastatic prostate cancer: An umbrella review of meta-analyses","authors":"Fausto Petrelli ,&nbsp;Francesca Trevisan ,&nbsp;Lorenza Bruschieri ,&nbsp;Valentina Riboldi ,&nbsp;Ivano Vavassori ,&nbsp;Silvia Seghezzi ,&nbsp;Andrea Esposito ,&nbsp;Lorenzo Dottorini ,&nbsp;Agostina De Stefani","doi":"10.1016/j.ctrv.2025.103064","DOIUrl":"10.1016/j.ctrv.2025.103064","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;The management of metastatic prostate cancer (mPC) has shifted from a purely systemic approach to an integrated paradigm incorporating local and metastasis-directed therapies. Advances in imaging and improved characterization of the &lt;em&gt;oligometastatic state&lt;/em&gt; have stimulated renewed interest in aggressive multimodal treatment strategies.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To systematically evaluate and grade the evidence from published &lt;em&gt;meta&lt;/em&gt;-analyses investigating the efficacy, safety, and credibility of local and metastasis-directed treatments in metastatic or oligometastatic prostate cancer.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Design, setting, and participants&lt;/h3&gt;&lt;div&gt;This umbrella review followed PRISMA 2020 recommendations and Ioannidis umbrella-review methodology. PubMed, Embase, Web of Science, and Cochrane Library were searched through June 2025. Eligible studies were systematic reviews or &lt;em&gt;meta&lt;/em&gt;-analyses with quantitative pooling of outcomes for local treatment (LT; prostate radiotherapy [RT] or radical prostatectomy [RP]), cytoreductive radical prostatectomy (CRP), or metastasis-directed therapy (MDT) using stereotactic body radiotherapy (SBRT). Twenty-one &lt;em&gt;meta&lt;/em&gt;-analyses published between 2018 and 2025, enrolling &gt; 160 000 patients, were included.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Outcome measurements and statistical analysis&lt;/h3&gt;&lt;div&gt;Primary endpoints were overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). Secondary endpoints included local control, toxicity, and prevention of symptomatic pelvic events. When multiple &lt;em&gt;meta&lt;/em&gt;-analyses assessed the same association, second-level pooling was performed. Evidence credibility was graded as &lt;em&gt;strong, highly suggestive, suggestive,&lt;/em&gt; or &lt;em&gt;weak.&lt;/em&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results and limitations&lt;/h3&gt;&lt;div&gt;Prostate RT improved OS in &lt;em&gt;low-volume metastatic hormone-sensitive disease&lt;/em&gt; (pooled HR ≈ 0.64–0.73) with minimal grade ≥ 3 toxicity (∼5%) and low heterogeneity (I&lt;sup&gt;2&lt;/sup&gt; ≈ 0 %). CRP demonstrated suggestive OS and CSS advantages (HR/OR ≈ 0.6–0.8; CSS ≈ 0.5) versus systemic therapy alone but no superiority over RT. MDT/SBRT significantly prolonged PFS (HR ≈ 0.48) and showed emerging OS benefit (HR ≈ 0.60) across randomized trials, with very low rates of serious toxicity (&lt;2%). Local therapy halved the risk of symptomatic pelvic complications (RR 0.50). Limitations include residual heterogeneity in imaging, disease definitions, and non-randomized data for surgical outcomes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Across 21 &lt;em&gt;meta&lt;/em&gt;-analyses, &lt;em&gt;prostate RT&lt;/em&gt; provides highly suggestive evidence of survival benefit in low-volume mHSPC, &lt;em&gt;CRP&lt;/em&gt; offers suggestive survival improvement in selected patients, and &lt;em&gt;MDT/SBRT&lt;/em&gt; achieves highly suggestive evidence for progression control with emerging OS benefit. These strategies represent validated, evidence-based components of modern mul","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"142 ","pages":"Article 103064"},"PeriodicalIF":10.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145758363","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":"2026-01-01","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":"2026-01-01","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}