Cancers最新文献

{"title":"From Thoracotomy to Robotic Platforms in Thoracic Surgery: Technical Evolution, Simulation-Based Training, and Surgical Outcomes.","authors":"Michele Piazzolla, Doroty Sampietro, Marco Donatello Delcuratolo, Paolo Nicola Camillo Girotti, Lucia Anna Muscarella, Paola Parente","doi":"10.3390/cancers18193193","DOIUrl":"10.3390/cancers18193193","url":null,"abstract":"<p><p>Thoracic surgery has progressively moved from open thoracotomy to video-assisted and robot-assisted approaches, reducing access-related trauma while changing the technical environment in which pulmonary resections are performed and taught. This narrative review examines the clinical evolution of open, video-assisted thoracic surgery (VATS), and robot-assisted thoracic surgery (RATS), with particular attention to the evidence supporting their perioperative and oncological outcomes, the learning curves associated with minimally invasive surgery, and the role of simulation-based training. Randomized trials now provide robust evidence that VATS improve postoperative recovery compared with thoracotomy in appropriately selected patients with predominantly early-stage non-small cell lung cancer, without compromising long-term oncological outcomes. Randomized comparisons between RATS and VATS support RATS as an oncologically acceptable minimally invasive alternative and suggest advantages in selected technical endpoints, particularly blood loss and lymph node retrieval, but do not demonstrate consistent superiority in major clinical or survival outcomes. Learning curves vary according to previous experience, case complexity, supervision, institutional volume, and the endpoint used to define competence, making fixed case-number thresholds an incomplete measure of proficiency. Simulation can improve selected technical skills and provide objective performance assessment, although evidence becomes progressively less robust when moving from simulator performance to operating room transfer and patient-level outcomes. Surgical approach, therefore, should be interpreted within a broader framework that includes patient and tumour characteristics, oncological quality, surgical expertise, institutional resources, and structured training.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ovarian Cyst Fluid as a Resource for Diagnostic and Prognostic Biomarker Discovery in Ovarian Lesions.","authors":"Lamia Sabry Aboelnasr, Nanki Deol, Yingran Jin Fu, Mona El-Bahrawy","doi":"10.3390/cancers18193182","DOIUrl":"10.3390/cancers18193182","url":null,"abstract":"<p><strong>Background/objectives: </strong>Differentiating benign, borderline, and malignant ovarian cystic lesions before surgery remains challenging, and many women undergo operations for lesions that prove benign. Most cystic lesions contain fluid that lies in direct contact with the lesion and forms part of the tumour microenvironment, potentially concentrating tumour-derived molecules diluted in the circulation. This review presents the current evidence on the value of ovarian cyst fluid analysis for the discovery of diagnostic and prognostic biomarkers across benign, borderline, and malignant lesions.</p><p><strong>Methods: </strong>We reviewed studies analysing ovarian cyst fluid using proteomic, glycoproteomic, metabolomic, inflammatory, and tumour-DNA approaches, together with conventional biomarkers and cytology, and considered pre-analytical and methodological factors affecting their interpretation.</p><p><strong>Results: </strong>Cyst fluid harbours proteins, glycoproteins, metabolites, cytokines, and DNA with tumour-specific mutations, frequently at concentrations exceeding those in matched serum. Multiple candidates discriminate malignant from benign lesions, and borderline lesions often show intermediate signatures. No single marker outperforms established CA125-based protocols, but multi-marker and multi-omics combinations have shown improved diagnostic performance within individual studies.</p><p><strong>Conclusions: </strong>Ovarian cyst fluid is a biologically enriched, underexploited substrate and a potential adjunct to existing diagnostic pathways. Realising its clinical potential will require standardised pre-analytics, validated multi-analyte panels, and prospective studies addressing clinical utility and reproducibility.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Same-Day Coordination of Mohs Surgery, Lymphoscintigraphy, and Sentinel Lymph Node Biopsy for Merkel Cell Carcinoma: A Single-Center Feasibility Report.","authors":"Victoria H Ruesch, Justin Thrush, James F Bena, Claudia Ricotti, Melissa Piliang, Melissa McEnery-Stonelake, Basia Marie Michalski-McNeely, Jon Meine, Jennifer Lucas, Christine Poblete-Lopez, Shlomo Koyfman, Brian Gastman, Allison T Vidimos","doi":"10.3390/cancers18193187","DOIUrl":"10.3390/cancers18193187","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor, most commonly occurring on the head and neck. Incidence of MCC is rising with the aging population. Five-year overall survival (OS) for localized MCC is 50.6%; 5-year OS for patients with distant metastases is 13.5%. The purpose of this study is to determine if coordination of care for the treatment of MCC is logistically feasible, and provide a description of the patient population observed at this institution. <b>Methods</b>: All patients with MCC diagnosis from January 2012-June 2024 were identified at our tertiary care center. All patients with MCC were added to our non-melanoma skin cancer registry. Outcomes were compared between those treated with our \"Merkel cell carcinoma in a day\" (MIAD) protocol and those receiving the standard treatment protocol. <b>Results</b>: No significant differences were detected in the recurrence rate, transit metastasis, distant metastasis, and disease-specific death. Nodal metastasis was higher in the MIAD group (HR 4.94, 95% CI 1.08-22.6, <i>p</i> = 0.039, six events total). Both groups had similar times to treatment and treatment within 30 days of diagnosis. <b>Conclusions</b>: MCC is a rare and aggressive tumor, often exhibiting subclinical tumor spread. Mohs micrographic surgery ensures 100% peripheral and deep margin assessment, with potential for tissue sparing. With thoughtful coordination, lymphoscintigraphy can be completed on the same day as Mohs surgery followed by sentinel lymph node biopsy (SLNB) and reconstructive surgery.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ubiquitination-Dependent Cyclin Regulation in Gastric Cancer and Emerging Targeted Therapies with Chinese Herbal Bioactive Compounds.","authors":"Sicheng Qian, Xinyi Zheng, Jiaqi Li, Jiahan Le, Jiangjiang Qin, Yitao Chen","doi":"10.3390/cancers18193179","DOIUrl":"10.3390/cancers18193179","url":null,"abstract":"<p><p>Gastric cancer (GC) remains one of the most prevalent malignancies worldwide, with a high mortality rate primarily attributable to late-stage diagnosis and limited therapeutic options. Aberrant cell proliferation arising from cell cycle dysregulation is a hallmark of GC pathogenesis. Cyclins, as core regulators of cell cycle progression, exhibit dynamic protein expression patterns that are tightly controlled by the ubiquitin-proteasome system (UPS). In GC, cyclins are frequently overexpressed due to impaired ubiquitination and subsequent proteasomal degradation. This review systematically elucidates the ubiquitination-mediated regulation of distinct cyclins (Cyclins D, E, A, and B) at specific cell cycle phases-G1, S, G2, and M-and highlights the critical roles of E3 ubiquitin ligases, including SCF complexes and APC/C, in GC progression. We further discuss how dysregulated non-coding RNAs and altered E3 ligase expression contribute to aberrant cyclin ubiquitination, thereby promoting GC cell proliferation, metastasis, and poor prognosis. Importantly, emerging evidence demonstrates that bioactive compounds derived from traditional Chinese medicine (TCM) can counteract these abnormalities by directly downregulating cyclin expression, modulating E3 ligase activity, or inhibiting 26S/20S proteasome function, thus restoring cell cycle homeostasis and suppressing GC growth. This review integrates molecular mechanisms of cyclin ubiquitination with TCM-based therapeutic strategies, offering novel insights into targeted interventions for GC.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunoglobulin A Subtype and Survival After Upfront Autologous Stem Cell Transplantation in Multiple Myeloma: A Real-World Cohort from the Bortezomib Era.","authors":"Tuba Güllü Koca, Nizameddin Koca, Fazıl Çağrı Hunutlu, Ahmet Mert Yanık, Sinem Çubukçu, Rümeysa Yılmaz, Tuba Ersal, Vildan Gürsoy, İbrahim Ethem Pınar, Vildan Özkocaman, Fahir Özkalemkaş","doi":"10.3390/cancers18193178","DOIUrl":"10.3390/cancers18193178","url":null,"abstract":"<p><strong>Background: </strong>Immunoglobulin isotype is recorded at diagnosis in every patient with intact-immunoglobulin multiple myeloma, but is not retained in the ISS, R-ISS, or R2-ISS.</p><p><strong>Methods: </strong>We analyzed 196 consecutive patients with IgA or IgG myeloma who underwent upfront autologous stem cell transplantation at a single center (2009-2023). The primary endpoint was progression-free survival (PFS); overall survival (OS) was the secondary endpoint. Cox models used information available at transplantation, including the induction regimen and transplant year, in the complete-case set (<i>n</i> = 131) and after multiple imputation (<i>n</i> = 196).</p><p><strong>Results: </strong>Median PFS was 14.8 versus 30.5 months and OS 43.2 versus 94.2 months in IgA versus IgG patients (both <i>p</i> < 0.001). IgA isotype was associated with inferior PFS (adjusted HR 1.85, 95% CI 1.13-3.02; imputed HR 1.83, 95% CI 1.22-2.73). For OS, the HR was 1.68 (0.98-2.88) in the complete-case analysis and 1.91 (1.24-2.94) after imputation, so its magnitude is uncertain. Models with maintenance gave 1.87 and 1.82. Progression documentation differed by maintenance status. Cytogenetic data were too incomplete to assess independence from genomic risk.</p><p><strong>Conclusions: </strong>In a bortezomib-era transplant cohort, IgA isotype was associated with inferior PFS; the association with OS was of uncertain magnitude. The finding is hypothesis-generating and requires validation in cohorts with complete cytogenetic characterization.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lymphatic Mapping to the Inguinal Region in Patients with Lower Extremity Melanoma Undergoing Radical Inguinal Lymph Node Dissection: A Retrospective Cohort Study.","authors":"Zhichao Tan, Yue Sun, Yunxiao Zhang, Zhengfu Fan, Chujie Bai, Shu Li, Tian Gao, Lu Zhang, Ruifeng Xue, Xinyu Wang, Mengmeng Liu, Hairui Wang, Jiayong Liu","doi":"10.3390/cancers18193184","DOIUrl":"10.3390/cancers18193184","url":null,"abstract":"<p><strong>Background/objectives: </strong>The anatomical distribution of inguinal lymph node (ILN) metastases may inform research on the extent of therapeutic dissection for lower-limb melanoma.</p><p><strong>Methods: </strong>Fifty-eight patients undergoing radical inguinal lymph node dissection (rILND) were retrospectively evaluated using five anatomical zones. Zone-specific node counts were reaggregated, and exploratory binary logistic regression assessed multiple-zone involvement.</p><p><strong>Results: </strong>The cohort included 48 clinically node-positive and 10 sentinel lymph node biopsy (SLNB)-positive patients. Among 816 mapped ILNs, 149 were positive. Zone I contained 102/149 positive nodes (68.5%); within-zone positivity was 102/303 (33.7%) in zone I, 27/243 (11.1%) in zone II, 13/190 (6.8%) in zone III, 3/39 (7.7%) in zone IV, and 4/41 (9.8%) in zone V. Five patients had no positive mapped ILNs. Zone I contained the only positive node in 19/20 patients (95.0%) and was the sole involved zone in 32/33 patients with single-zone involvement (97.0%). Twenty patients had multiple-zone involvement. In a two-variable complete-case model (50 patients; 18 events), ≥3 positive ILNs remained associated with multiple-zone involvement (adjusted odds ratio, 34.80; 95% confidence interval, 5.88-206.08), whereas extranodal extension did not.</p><p><strong>Conclusions: </strong>This small, selected cohort provides preliminary pathological evidence of preferential inferior-zone involvement. It does not establish sequential spread or the oncological safety of reduced rILND. External and prospective validation are required.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic Inflammation and Colorectal Cancer: Assessing the Role of Reverse Causality.","authors":"Fatemeh Safizadeh, Tafirenyika Gwenzi, Marko Mandic, Michael Hoffmeister, Hermann Brenner","doi":"10.3390/cancers18193190","DOIUrl":"10.3390/cancers18193190","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Prospective studies have reported associations between systemic inflammatory biomarkers and colorectal cancer (CRC) risk, but whether these reflect a causal role of inflammation or responses to preclinical disease remains uncertain. <b>Methods</b>: Using data from 383,850 UK Biobank participants (aged 40-69 years; recruited 2006-2010), we investigated potential reverse causality by assessing these associations according to time since biomarker assessment. Baseline systemic inflammatory markers, including C-reactive protein (CRP), albumin, and blood cell-derived ratios, were assessed. Multivariable Cox models estimated associations with CRC risk across predefined follow-up intervals. <b>Results</b>: Over a median follow-up of 11.8 years, 4996 participants developed CRC. Inflammatory biomarkers were associated with increased CRC risk, particularly during the early follow-up. Associations weakened substantially or disappeared when early follow-up was excluded. For example, CRP was associated with a 3.03-fold higher CRC risk (highest vs. lowest quartile; 95% CI: 2.06-4.45) within the 0-1-year interval, while no association was observed during the 3-5, 6-8, or >8-year intervals. Across complete follow-up, the association remained statistically significant but much weaker (HR: 1.17; 95% CI: 1.07-1.28). Similar patterns were observed for most other biomarkers, except the platelet-to-neutrophil ratio. <b>Conclusions</b>: Our results suggest that the associations between inflammatory biomarkers and CRC risk may partly reflect reverse causality arising from preclinical disease.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Markers in Triple-Negative Breast Cancer (TNBC).","authors":"Ishaan Shah, Srushti Naik, Frank Arfuso, Sudha Warrier, Arun Dharmarajan, Sonal M Manohar","doi":"10.3390/cancers18193181","DOIUrl":"10.3390/cancers18193181","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is a highly aggressive and molecularly diverse subtype of breast cancer characterized by the absence of estrogen, progesterone, and human epithelial growth factor receptors. Despite advancements in therapeutic interventions, TNBC continues to remain associated with high metastatic potential, high likelihood of recurrence, and importantly, poor prognosis. Therefore, validated prognostic biomarkers are needed that can facilitate accurate prognostic assessment, drive treatment options, and lead to better clinical outcomes. This comprehensive review aims to provide a detailed overview of established and emerging prognostic biomarkers in TNBC, highlighting their biological relevance, clinical utility, and translational potential. We initially focus on the different classes of individual prognostic biomarkers and their limitations as far as prognostic stratification is concerned. We then move toward the development of multi-marker panels, further taking into account the critical factors limiting their clinical implementation. Development of standardized, clinically validated, and cost-effective multi-marker prognostic frameworks that can integrate the different aspects of tumor biology is the need of the hour. Such comprehensive approaches are expected to enhance prognostication and thereby improve outcomes in TNBC patients.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic Priming with Oral Decitabine/Cedazuridine Combined with Nivolumab in Unresectable or Metastatic Mucosal Melanoma: Clinical and Correlative Findings from a Phase Ib/II Trial.","authors":"Jessica S W Borgers, Cheng-Chang Wu, Theresa M Medina, Claire M Muckle, Elizabeth N Katsnelson, Phaedra A Whitty, Luke Mantle, Sapna P Patel, Dexiang Gao, Kimberly R Jordan, William A Robinson, Richard P Tobin, Martin D McCarter, Kasey L Couts","doi":"10.3390/cancers18193172","DOIUrl":"10.3390/cancers18193172","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Mucosal melanoma is a rare, aggressive melanoma subtype with lower response rates to immune checkpoint inhibitors than cutaneous melanoma. We previously identified reduced expression of innate immune pathogen-sensing pathway genes in mucosal melanoma, including components of the retinoic acid-inducible gene-I (RIG-I) pathway, and found that decitabine can induce re-expression of these immune genes and tumor-associated antigens. This study evaluated epigenetic immune priming with oral decitabine/cedazuridine (DEC-C) combined with nivolumab in patients with unresectable or metastatic mucosal melanoma. <b>Methods:</b> NCT05089370 was an open-label, single-center, single-arm phase Ib/II trial. Patients received DEC-C (35 mg decitabine/100 mg cedazuridine) orally for five days followed by nivolumab 480 mg every four weeks. The primary endpoint was safety and determination of the recommended phase II dose (RP2D). Secondary endpoints included objective response rate (ORR) and survival outcomes. Exploratory endpoints assessed immune and epigenetic correlates. <b>Results:</b> Eight patients were enrolled. Treatment-related adverse events occurred in seven patients (88%), with dose-limiting toxicities observed in three (38%). The RP2D was not established due to premature trial closure. At data cut-off, two patients remained on treatment with ongoing partial responses. The ORR was 25% (95% CI, 3.2-65), median progression-free survival was 3.0 months (95% CI, 2.1-not reached), and median overall survival was 7.2 months (95% CI, 4.4-not reached). Treatment significantly decreased global DNA methylation and induced RIG-I pathway genes in circulating immune cells. <b>Conclusions:</b> DEC-C plus nivolumab was associated with frequent treatment-related toxicities consistent with the known safety profiles of decitabine and nivolumab and demonstrated on-target epigenetic and immune activity in circulating cells. Although two partial responses were observed, the small sample size and wide confidence interval preclude conclusions regarding efficacy. These findings support future biomarker-integrated studies evaluating epigenetic immune-priming combinations in mucosal melanoma, with prospective optimization of dose, schedule, and treatment setting.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Evidence as a Driver of Precision Oncology and Personalized Therapeutic Sequencing in Later-Line Metastatic Colorectal Cancer.","authors":"Carlo Signorelli","doi":"10.3390/cancers18193174","DOIUrl":"10.3390/cancers18193174","url":null,"abstract":"<p><p><b>Background:</b> The therapeutic landscape of refractory metastatic colorectal cancer (mCRC) has expanded with antiangiogenic agents, cytotoxic therapies, immunotherapy, and biomarker-driven treatments. Randomized clinical trials (RCTs) establish efficacy and safety, while real-world evidence (RWE) can complement them by addressing generalizability, treatment delivery, safety, and outcomes in populations underrepresented in prospective studies. This narrative review examines the contribution and limitations of RWE in precision oncology and later-line therapeutic sequencing in mCRC. <b>Methods:</b> We reviewed evidence from randomized trials, observational studies, real-world registries, translational research, and contemporary international guidance, focusing on later-line antiangiogenic strategies, trifluridine/tipiracil-based treatment, fruquintinib, anti-EGFR rechallenge, immunotherapy in MSI-H/dMMR disease, and targeted therapies for actionable molecular alterations. Particular attention was given to RWE methodology and interpretation. <b>Results:</b> RWE complements randomized evidence by characterizing effectiveness and toxicity in heterogeneous populations, treatment delivery and dose modification, and implementation of biomarker-guided strategies in routine practice. Observational studies may also inform therapeutic sequencing and identify prognostic or pharmacodynamic correlates, although causal interpretation is limited by selection bias, treatment attrition, time-dependent and residual confounding. Longitudinal circulating tumor DNA (ctDNA) assessment is particularly relevant to molecular reassessment and anti-EGFR rechallenge, while broader ctDNA-guided adaptive treatment strategies remain investigational. <b>Conclusions:</b> Later-line mCRC management increasingly integrates molecular profiling, treatment history, patient fitness, toxicity, and therapeutic sequencing. High-quality RWE provides complementary evidence on how these strategies perform and are implemented in routine practice but should be interpreted according to study design and susceptibility to bias. Integration of rigorous RWE with randomized and prospective molecular evidence may help bridge the gap between trial efficacy and real-world effectiveness and support individualized later-line care.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}