Current Opinion in Oncology最新文献

{"title":"Implementing liquid biopsy in HR+/HER2- metastatic breast cancer: challenges and opportunities.","authors":"Valentina Frescura, Massimo Cristofanilli, Carolina Reduzzi, Letizia Pontolillo, Eleonora Nicolò","doi":"10.1097/CCO.0000000000001267","DOIUrl":"10.1097/CCO.0000000000001267","url":null,"abstract":"<p><strong>Purpose of review: </strong>Liquid biopsy (LB) is rapidly transforming the management of hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancer (mBC). In this review, we discuss the most recent findings on circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), exploring their roles across the treatment continuum, from treatment selection to resistance monitoring.</p><p><strong>Recent findings: </strong>ctDNA-based detection of actionable mutations - including ESR1 and PIK3CA - achieved regulatory validation as a primary predictive biomarker for treatment selection, supporting the approval of novel endocrine agents and targeted therapies in HR+/HER2- mBC. Serial ctDNA monitoring demonstrated the ability to intercept emerging resistance mechanisms ahead of radiological progression, opening a window for preemptive therapeutic adaptation. CTCs enumeration maintains robust independent prognostic value, with emerging evidence supporting its role in guiding treatment escalation and de-escalation decisions. Integrated multiparametric LB approaches combining CTCs and ctDNA are crucial to improve prognostic accuracy and clinical decision-making.</p><p><strong>Summary: </strong>LB is progressively shifting from a research tool to a clinical decision-making instrument in HR+/HER2- mBC. Prospective interventional trials, methodological standardization, and integrated strategies are needed to fully translate its potential into improved patient outcomes.</p>","PeriodicalId":10893,"journal":{"name":"Current Opinion in Oncology","volume":" ","pages":"496-505"},"PeriodicalIF":2.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time-of-day administration of immune checkpoint inhibitors: current clinical evidence and future directions for breast cancer.","authors":"Rui Kitadai, Filipa Lynce, Ana C Garrido-Castro","doi":"10.1097/CCO.0000000000001270","DOIUrl":"10.1097/CCO.0000000000001270","url":null,"abstract":"<p><strong>Purpose of review: </strong>Immune checkpoint inhibitors (ICIs) are increasingly used in breast cancer, particularly in triple-negative breast cancer. This review summarizes the biologic rationale and emerging clinical evidence for time-of-day ICI administration and discusses its implications for breast cancer.</p><p><strong>Recent findings: </strong>Circadian rhythms provide a biologic rationale for time-dependent immunotherapy efficacy. Several retrospective studies across multiple tumor types have suggested associations between earlier ICI administration and improved outcomes, although findings remain inconsistent. Breast cancer-specific data are expanding but remain heterogeneous, with signals varying by treatment setting, endpoint, timing definition, and tumor immune contexture. These findings suggest that treatment timing should be interpreted in the context of the broader treatment platform in which immunotherapy is delivered, including concomitant chemotherapy and supportive medications, as well as host circadian state and tumor immune contexture. An ongoing prospective study aims to integrate circadian, systemic immune, and tumor-based assessments to elucidate the biological and clinical relevance of treatment timing in breast cancer.</p><p><strong>Summary: </strong>Current evidence does not establish an optimal infusion window for breast cancer treatment. Prospective studies integrating clinical outcomes with circadian, systemic immune, and tumor-based analyses are needed to determine whether treatment timing can be developed into a biologically informed strategy.</p>","PeriodicalId":10893,"journal":{"name":"Current Opinion in Oncology","volume":" ","pages":"471-478"},"PeriodicalIF":2.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electronic patient-reported outcomes platforms to shift from episodic to continuous oncology in breast cancer.","authors":"Thanate Dajsakdipon, Luca Formenti, Emanuela Ferraro, Giuseppe Curigliano, Dario Trapani","doi":"10.1097/CCO.0000000000001272","DOIUrl":"10.1097/CCO.0000000000001272","url":null,"abstract":"<p><strong>Purpose of review: </strong>To critically examine the clinical value of patient-reported outcomes (PROs) assessed through electronic tools (ePROs) in breast cancer, with a focus on their impact on patient management and real-world implementation.</p><p><strong>Recent findings: </strong>Accumulating evidence indicates that ePRO-based symptom monitoring improves patient-clinician communication, reduces symptom burden, and decreases acute healthcare utilization. While improvements in quality of life are consistently observed across studies, evidence for survival benefit remains context-dependent and is largely derived from heterogeneous oncology populations. Notably, the effectiveness of ePROs appears to depend less on digitalization itself and more on structured implementation, including alert systems, timely clinical response, demanding implementation efforts, and preparedness and resilience of the digital health infrastructure.</p><p><strong>Summary: </strong>ePROs represent a shift from episodic, visit-based assessment to more continuous and responsive monitoring in breast cancer care. Their clinical value is strongest when integrated into care pathways with clearly defined responsibilities and actionable workflows. Future development should focus on scalable models that balance efficiency with sustained patient engagement and equitable access.</p>","PeriodicalId":10893,"journal":{"name":"Current Opinion in Oncology","volume":" ","pages":"429-440"},"PeriodicalIF":2.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paraneoplastic neurological syndromes: an update on incidence, antibody discovery, and testing.","authors":"Giulia Berzero","doi":"10.1097/CCO.0000000000001268","DOIUrl":"10.1097/CCO.0000000000001268","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review aims to provide a summary of the latest novelties in the field of paraneoplastic neurological syndromes (PNS), emphasizing relevant clinical updates on epidemiology, antibody discovery, and testing.</p><p><strong>Recent findings: </strong>Population-based studies have provided estimates of PNS incidence in the United States and Europe. A wider availability of commercial and in-house antibody testing, together with the discovery of novel antibodies, was pinpointed as a possible reason for the progressive increase in PNS incidence observed in recent years. Updated diagnostic criteria for PNS diagnosis published in 2021 were validated in cohorts of adults and children, showing improved sensitivity and similar specificity compared to the 2004 criteria. Laboratory studies have highlighted the pitfalls of commercial and in-house assays for antibody detection, underscoring the importance of sample referral to reference centers for additional analyses in selected cases. Novel antibodies to intracellular and cell-surface antigens associated with paraneoplastic encephalitis (NIF, ZSCAN1, septin-7, PDE10A, CAMKV), cerebellar syndrome (e.g. TRIM46, TRIM9/67, SEZ6L2, RGS8, mGluR2), and brainstem encephalitis (KELCH11, LUZP4) were described and related to recurring cancer types, expanding the PNS spectrum.</p><p><strong>Summary: </strong>The present review provides an update on PNS, including novel antibodies and phenotypes.</p>","PeriodicalId":10893,"journal":{"name":"Current Opinion in Oncology","volume":" ","pages":"506-514"},"PeriodicalIF":2.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148911187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precision medicine for pediatric gliomas.","authors":"Lorena V Baroni, Eric Bouffet","doi":"10.1097/CCO.0000000000001277","DOIUrl":"10.1097/CCO.0000000000001277","url":null,"abstract":"<p><strong>Purpose of review: </strong>The fifth edition of the WHO Classification of Tumors of the Central Nervous System marked a paradigm shift from predominantly histopathological classification toward integrated molecular-pathological definitions. This review summarizes the contemporary molecular landscape of pediatric gliomas, pivotal clinical trial data, current indications for targeted therapies, and major challenges to effective precision treatment, including adaptive resistance and blood-brain barrier penetration.</p><p><strong>Recent findings: </strong>Sporadic pediatric low-grade gliomas (pLGGs) are characterized by alterations activating the RAS-mitogen-activated protein kinase (MAPK) pathway, particularly BRAF fusions and V600E mutations, enabling the integration of targeted therapies into frontline treatment. Among high-grade tumors, infant-type hemispheric gliomas represent a favorable, fusion-driven subgroup characterized by recurrent receptor tyrosine kinase alterations involving ALK, NTRK1/2/3, ROS1, and MET , with remarkable sensitivity to selective inhibitors. In contrast, pediatric-type diffuse high-grade gliomas (pHGGs) and diffuse midline gliomas (DMGs) in older children remain highly refractory and are frequently driven by epigenetic dysregulation associated with histone H3 G34 and H3 K27 alterations.</p><p><strong>Summary: </strong>Targeted therapies have an expanding role in the management of pediatric low- and high-grade gliomas. Further research is particularly needed for pHGGs and DMGs, where outcomes remain unsatisfactory and effective therapeutic options are limited.</p>","PeriodicalId":10893,"journal":{"name":"Current Opinion in Oncology","volume":" ","pages":"524-531"},"PeriodicalIF":2.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149007730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The next-generation biomarkers in early-stage triple negative breast cancer.","authors":"Federica Falcone, Erica Pietroluongo, Pietro De Placido","doi":"10.1097/CCO.0000000000001266","DOIUrl":"10.1097/CCO.0000000000001266","url":null,"abstract":"<p><strong>Purpose of review: </strong>Despite maximal neoadjuvant chemoimmunotherapy, nearly 40% of early-stage triple-negative breast cancer (TNBC) patients fail to achieve pathological complete response, underscoring an urgent need for biomarkers capable of guiding treatment modulation. This review summarizes recent advances in tumor-infiltrating lymphocytes (TILs), circulating tumor DNA (ctDNA), and genomic signatures, exploring their potential integration into clinical decision-making.</p><p><strong>Recent findings: </strong>TILs remain the most validated, cost-effective prognostic biomarker, although standardized scoring is still needed to overcome interobserver variability. ctDNA has emerged as a dynamic, real-time prognostic tool, with postneoadjuvant detection strongly predicting relapse and worse outcomes. Nonetheless, optimal sampling timing remains undefined. Genomic signatures, particularly TNBC-DX, provide standardized, reproducible prognostic information by integrating immune and proliferative gene expression. Emerging data suggest that combining these biomarkers may offer a complementary and synergistic effect.</p><p><strong>Summary: </strong>Multibiomarker integration, supported by prospective validation and automated models, represents a promising approach to personalize treatment algorithms in early-stage TNBC, balancing efficacy and toxicity while guiding escalation and de-escalation strategies.</p>","PeriodicalId":10893,"journal":{"name":"Current Opinion in Oncology","volume":" ","pages":"489-495"},"PeriodicalIF":2.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adjuvant treatments for stage I breast cancers of one centimeter or less.","authors":"Letizia Matera, Carmine Valenza, Giuseppe Curigliano","doi":"10.1097/CCO.0000000000001274","DOIUrl":"10.1097/CCO.0000000000001274","url":null,"abstract":"<p><strong>Purpose of review: </strong>The increasing detection of subcentimetric breast cancers (BC) through widespread implementation of mammographic screening has raised important questions regarding the optimal management of patients with stage I tumors measuring ≤1 cm in the adjuvant setting. Although these tumors exhibit an overall excellent prognosis, outcomes are heterogeneous and influenced by biological factors and patients characteristics. This review summarizes current evidence on adjuvant systemic treatments and discusses emerging approaches to treatment individualization.</p><p><strong>Recent findings: </strong>Evidence supporting adjuvant systemic treatments in subcentimetric stage I BC remains limited, as these tumors have been underrepresented in most pivotal clinical trials and current recommendations are partly based on retrospective evidence. In hormone receptor-positive disease, endocrine therapy remains the cornerstone of treatment, while chemotherapy could be considered according to genomic assays, in selected cases. In HER2-positive tumors, trastuzumab-based de-intensified regimens have demonstrated excellent outcomes. In triple-negative BC, chemotherapy appears to provide the greatest benefit in selected higher-risk tumors.</p><p><strong>Summary: </strong>Treatment decisions in subcentimetric stage I BC should incorporate biological characteristics and patient factors beyond tumor size. Ongoing treatment optimization trials, together with integrated risk prediction models and emerging biomarkers, including circulating tumor DNA and tumor-infiltrating lymphocytes, may improve patient selection for treatment modulation strategies aimed at maximizing benefit while minimizing unnecessary toxicity.</p>","PeriodicalId":10893,"journal":{"name":"Current Opinion in Oncology","volume":" ","pages":"449-460"},"PeriodicalIF":2.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibody-drug conjugates in breast cancer: the first-line and curative setting.","authors":"Nicole Odzer, Paolo Tarantino","doi":"10.1097/CCO.0000000000001265","DOIUrl":"10.1097/CCO.0000000000001265","url":null,"abstract":"<p><strong>Purpose of review: </strong>Antibody-drug conjugates (ADCs) have rapidly advanced from later-line salvage therapy into first-line metastatic and curative perioperative settings. This review appraises recent practice-changing data that collectively redefined treatment standards across Human epidermal growth factor receptor 2 (HER2)-positive, triple-negative, and hormone receptor-positive/HER2-negative breast cancer.</p><p><strong>Recent findings: </strong>Three trials, DESTINY-Breast09, DESTINY-Breast05, and DESTINY-Breast11, established the role of T-DXd across first-line metastatic and perioperative HER2-positive settings, with both early breast cancer indications receiving FDA approval in May 2026. In triple-negative disease, ASCENT-04/KEYNOTE-D19 established sacituzumab govitecan plus pembrolizumab as new first-line option for Programmed cell death ligand 1 (PD-L1)-positive metastatic TNBC. Meanwhile, TROPION-Breast02 had led to the approval of Datopotamab deruxtecan (Dato-DXd) for the first-line treatment of immunotherapy-ineligible patients with metastatic TNBC, whereas ASCENT-03 led to the NCCN incorporation of first-line sacituzumab govitecan for the same population. Multiple further neoadjuvant and adjuvant ADC trials are expected to further reshape treatment algorithms over the coming years.</p><p><strong>Summary: </strong>ADCs now hold regulatory and guideline approval as preferred first-line options across all major breast cancer subtypes, in both the metastatic and curative perioperative settings. Proactive ILD surveillance is essential across all approved agents. Remaining challenges include sequencing among topoisomerase I inhibitor-payload ADCs and awaiting mature survival readouts from perioperative trials.</p>","PeriodicalId":10893,"journal":{"name":"Current Opinion in Oncology","volume":" ","pages":"441-448"},"PeriodicalIF":2.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging role of targeted therapy in drug-resistant epilepsy in patients with glioma.","authors":"Francesco Bruno, Alessia Pellerino, Roberta Rudà","doi":"10.1097/CCO.0000000000001279","DOIUrl":"10.1097/CCO.0000000000001279","url":null,"abstract":"<p><strong>Purpose of review: </strong>Seizures are among the most frequent and disabling manifestations of gliomas, and in some patients remain drug-resistant despite optimal antiseizure medication and standard antitumour treatments. This review examines the clinical evidence that targeted therapies may improve seizure control in patients with glioma.</p><p><strong>Recent findings: </strong>The strongest signal comes from mutant isocitrate dehydrogenase (IDH1/2) inhibition. In the phase 3 INDIGO trial, exploratory and posthoc analyses showed an on-treatment seizure rate of 18.2 per person-year with vorasidenib vs. 51.2 with placebo [rate ratio 0.36, 95% confidence interval (CI) 0.14-0.89]. Emerging real-world series and individual case reports support these findings, and preclinical work indicates an antiseizure effect at least partly independent of tumour control. BRAF/MEK inhibition and mTOR inhibition have an established antitumour role in circumscribed astrocytic and glioneuronal tumours, and everolimus reduces both tumour volume and pharmacoresistant seizures in tuberous sclerosis complex. Beyond genotype, the shared circuitry of tumourigenesis and epileptogenesis, such as neuron-glioma synapses, has generated a second wave of candidate targets, none yet clinically validated.</p><p><strong>Summary: </strong>Targeted agents are emerging as disease-modifying options that may also reduce seizure burden, but seizure freedom must be tested in future trials as a prespecified endpoint rather than inferred from exploratory analyses.</p>","PeriodicalId":10893,"journal":{"name":"Current Opinion in Oncology","volume":" ","pages":"515-523"},"PeriodicalIF":2.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond poly(ADP-ribose) polymerase inhibition: emerging therapeutic strategies for germline BRCA1/2 -mutated and PALB2 -mutated breast cancers.","authors":"Julian David Etessami, Laura Tori, Marta Aconito, Antonio Marra, Giuseppe Curigliano","doi":"10.1097/CCO.0000000000001275","DOIUrl":"10.1097/CCO.0000000000001275","url":null,"abstract":"<p><strong>Purpose of review: </strong>Germline or somatic biallelic inactivation of BRCA1 , BRCA2 and PALB2 genes define a clinically and biologically distinct subset of breast cancers characterized by homologous recombination deficiency (HRD) and sensitivity to PARP inhibitors. Despite regulatory approvals of olaparib and talazoparib for breast cancers in patients harboring germline BRCA1 and BRCA2 pathogenic/likely pathogenic variants, therapeutic progress in this setting has been limited by therapeutic resistance and treatment-related toxicity. This review studied emerging therapeutic strategies aimed at extending the clinical benefit of PARP inhibition and exploring novel vulnerabilities in HRD-associated breast cancer.</p><p><strong>Recent findings: </strong>Resistance to PARP inhibitors can arise through multiple mechanisms, including reversion mutations, restoration of homologous recombination, replication fork stabilization, and upregulation of drug efflux transporters. Importantly, none of these mechanisms has been validated as a clinical biomarker so far. Emerging strategies include next-generation PARP1-selective inhibitors with improved therapeutic windows, rational combinations with CDK4/6 inhibitors, antibody-drug conjugates, immune checkpoint inhibitors, and PI3K/AKT pathway inhibitors. Novel synthetic lethal approaches targeting polymerase theta (POLQ), ATR, WEE1, EZH2, and ATM are also under active investigation, with early clinical evidence of activity in DNA damage response-deficient tumors.</p><p><strong>Summary: </strong>The expanding landscape of therapeutic options in patients with either germline or somatic genetic alterations of BRCA1 and BRCA2 , as well as other homologous recombination genes, offers significant opportunities to improve outcomes beyond first-generation PARP inhibition. Translational research to define resistance biomarkers, optimize combination strategies, and validate PALB2 as a fully equivalent therapeutic target remain a priority.</p>","PeriodicalId":10893,"journal":{"name":"Current Opinion in Oncology","volume":" ","pages":"479-488"},"PeriodicalIF":2.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149007711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}