Cancers最新文献

{"title":"Long-Term Outcomes Following Reconstruction of Diaphyseal Defects of the Upper and Lower Extremities Using Diaphyseal Implants: A Retrospective Study with Focus on Fixation Technique.","authors":"Tymoteusz Budny, Anna Maria Rachbauer, Georg Gosheger, Felix Lückel, Marieke De Vaal, Sebastian Klingebiel, Jan Christoph Theil, Niklas Deventer","doi":"10.3390/cancers17183059","DOIUrl":"10.3390/cancers17183059","url":null,"abstract":"<p><p><b>Background:</b> The reconstruction of diaphyseal bone defects following tumor resection offers various biological and endoprosthetic treatment options. The present study analyzes the impact of the fixation method (cemented; uncemented; with locking screw; without locking screw) of the diaphyseal implant on clinical outcomes. Factors such as patient age and weight as well as tumor type and location are also considered. <b>Methods:</b> This study included 39 patients who underwent intercalary endoprosthetic reconstruction of the humerus (n = 4); femur (n = 29); and tibia (n = 6) between 1998 and 2020. Prosthetic complications, fixation methods and the MSTS score for functional outcome were statistically analyzed using SPSS and R. <b>Results:</b> The event-free probability in the competing risk model was 61% (95% CI 43-74%) after one year and 11% (95% CI 3-28%) after five years. The complication rate in the patient cohort was 54%. Cementless prosthesis fixation was associated with a statistically significant better functional outcome. Additionally, higher body weight and older patient age were associated with lower MSTS scores. <b>Conclusions:</b> Patients requiring rapid remobilization or adjuvant radiation therapy may benefit more from diaphyseal implants compared to biological reconstructions. However, the complication and revision rates of diaphyseal implants are elevated. The chosen fixation method shows a statistically significant influence on functional outcome.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173888","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":"Evolution of Perioperative Outcomes in Robot-Assisted Radical Cystectomy over 20 Years of Experience in a High-Volume Tertiary Robotic Center.","authors":"Simone Morra, Stefano Resca, Nicola Frego, Sara Tamburini, Marco Ticonosco, Alessandro Pissavini, Andrea Noya Mourullo, Francesco Barletta, Mario de Angelis, Edward Lambert, Frederiek D'Hondt, Ruben De Groote, Geert De Naeyer, Alexandre Mottrie","doi":"10.3390/cancers17183060","DOIUrl":"10.3390/cancers17183060","url":null,"abstract":"<p><strong>Background/objectives: </strong>Robot-assisted radical cystectomy (RARC) has demonstrated improved perioperative outcomes and recovery in bladder cancer (BCa) patients. This study compares patient and tumor characteristics, operative time (OT), length of stay (LOS), and complication rates between a historical (2003-2016) and a contemporary cohort (2017-2024) treated at a high-volume robotic center.</p><p><strong>Methods: </strong>Data from 274 BCa patients who underwent RARC at AZORG Hospital, Aalst, Belgium, were analyzed. Perioperative outcomes were compared between cohorts. Multivariable Poisson regression models identified predictors of longer OT and LOS, while multivariable logistic regression models (MLRMs) assessed predictors of higher complication rates.</p><p><strong>Results: </strong>Overall, 274 BCa patients who underwent RARC were identified (38% historical cohort vs. 62% contemporary cohort). The contemporary cohort had a significantly shorter median OT (345 vs. 360 min; <i>p</i> = 0.048) and LOS (8 vs. 12 days; <i>p</i> < 0.001) compared to the historical cohort. Postoperative complications were lower in the contemporary group, with more cases experiencing no complications (60% vs. 41%) and fewer grade 3-4 complications (10% vs. 27%; <i>p</i> < 0.001). In multivariable Poisson regression, the contemporary cohort was an independent predictor of shorter OT (Incidence Rate Ratio [IRR]: 0.94, 95% [Confidence Interval] CI: 0.93-0.96; <i>p</i> = 0.04) and shorter LOS (IRR: 0.65, 95% CI: 0.60-0.69; <i>p</i> < 0.001). In MLRMs predicting complications, the contemporary cohort was associated with lower risk (Odds Ratio: 0.42, 95% CI: 0.23-0.76; <i>p</i> = 0.005).</p><p><strong>Conclusions: </strong>RARC outcomes improved significantly over time, with reduced OT, LOS, and complication rates in the contemporary cohort, highlighting advancements in surgical techniques, perioperative care, and patient safety. These findings reinforce the role of RARC in optimizing BCa treatment.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173940","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":"IDH Mutations and Intraoperative 5-ALA Fluorescence in Gliomas: A Systematic Literature Review with Novel Exploratory Hypotheses on the Modulatory Effect of Vorasidenib.","authors":"Magdalena Rybaczek, Marek Jadeszko, Aleksander Lebejko, Magdalena Sawicka, Zenon Mariak, Tomasz Łysoń, Halina Car, Przemysław Wielgat","doi":"10.3390/cancers17183075","DOIUrl":"10.3390/cancers17183075","url":null,"abstract":"<p><p><b>Background</b>: Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) enables the intraoperative visualization of glioma. However, its effectiveness varies based on tumor subtype and molecular profile, posing challenges for achieving complete resection. Our systematic review aims to explore the relationship between IDH mutation status and intraoperative fluorescence visualization. Importantly, this is the first study to propose that vorasidenib, an emerging IDH-targeting agent, could enhance 5-ALA-guided surgery, marking a novel direction for translational research. <b>Methods</b>: A systematic literature search was conducted using the PubMed, Cochrane Library, Scopus and Web of Science databases up to May 2025, following PRISMA guidelines. The primary outcomes included fluorescence detection rates across different glioma subtypes and their correlation with IDH mutation status. Secondary outcomes comprised surgical efficacy measures such as gross total resection (GTR), overall survival (OS), and progression-free survival (PFS). Additionally, we analyzed the metabolic consequences of IDH mutations and evaluated the potential role of vorasidenib in enhancing 5-ALA-induced fluorescence. <b>Results</b>: Seven studies including 621 patients included in the final analysis. Fluorescence detection was nearly universal in WHO grade 4 gliomas (94-100%), but lower in grade 3 (43-85%) and rare in grade 2 (7-26%). Several cohorts reported reduced fluorescence in IDH-mutant gliomas, although this was not consistent across all studies. In high-grade gliomas, visible fluorescence correlated with higher GTR rates and, in some series, longer OS. Conversely, in lower-grade IDH-mutant gliomas, fluorescence did not increase GTR and was associated with worse PFS and OS. <b>Conclusions</b>: The effectiveness of 5-ALA-guided fluorescence in glioma surgery is significantly influenced by both tumor grade and IDH mutation status. Vorasidenib may represent a potential avenue for modulating tumor metabolism and enhancing intraoperative fluorescence in IDH-mutant gliomas, a hypothesis that warrants further experimental validation.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12469012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173544","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":"Impact of Endocrine Therapy for Cancer on Periodontal Health: A Systematic Review.","authors":"Federica Romano, Francesco Franco, Barbara Mognetti, Giovanni Nicolao Berta","doi":"10.3390/cancers17183066","DOIUrl":"10.3390/cancers17183066","url":null,"abstract":"<p><p><b>Background/Objectives</b>: With the growing number of cancer survivors receiving long-term endocrine therapy, understanding its potential effects on oral and periodontal health is of increasing clinical relevance. This systematic review aimed to synthesize current evidence on the impact of hormone therapies used in cancer treatment on periodontal status. <b>Methods</b>: A comprehensive literature search was conducted across the Medline, Web of Science, and Scopus databases to identify observational studies published up to June 2025 that evaluated the effects of endocrine therapy on periodontal parameters and tooth loss in cancer patients. <b>Results</b>: Thirteen studies met the inclusion criteria, twelve involving breast cancer patients and one prostate cancer. Third-generation aromatase inhibitors (AIs) were the most frequently studied agents, either alone or in comparison with tamoxifen. Most studies reported that AI therapy was associated with a higher prevalence of severe periodontitis, increased bleeding on probing and more severe alveolar bone loss compared to healthy controls. In contrast, tamoxifen appeared to have a comparatively milder impact on periodontal health. The single study on prostate cancer patients undergoing androgen deprivation therapy similarly indicated a higher prevalence of periodontitis with respect to controls. <b>Conclusions</b>: These findings suggest a potential link between endocrine therapy and periodontal status deterioration, particularly with AIs. This review highlights an important yet often neglected aspect of survivorship care and emphasizes the need for routine periodontal assessment and interdisciplinary collaboration in the management of patients undergoing hormone therapy for cancer.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173682","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":"Head and Neck Cancer in Fanconi Anemia: Clinical Challenges and Molecular Insights into a DNA Repair Disorder.","authors":"Juhye Choi, Moonjung Jung","doi":"10.3390/cancers17183046","DOIUrl":"10.3390/cancers17183046","url":null,"abstract":"<p><p>Fanconi anemia (FA) is a genetic disorder characterized by congenital anomalies, bone marrow failure, and cancer predisposition. Among other solid cancers, head and neck squamous cell carcinoma (FA HNSCC) is the most common cancer type in individuals with FA. The FA pathway is required for the complete repair of DNA interstrand crosslinks (ICLs), and unresolved ICLs result in cell cycle arrest, apoptosis, or complex chromosomal rearrangements due to chromosome breaks, ultimately leading to tumorigenesis. FA HNSCCs present earlier (median age of onset in the 30s) and exhibit a more aggressive course with frequent recurrence and second primaries, and entail a poorer survival rate compared to sporadic HNSCC. FA HNSCCs are mostly human papillomavirus (HPV)-negative and frequently carry somatic copy number variations (CNVs), which amplify oncogenes implicated in sporadic HNSCC, but single-nucleotide variants or small insertions and deletions are less frequent than in HPV-negative sporadic HNSCC. A subset of sporadic HNSCC carries pathogenic mutations or promoter methylation in FA genes, which also harbor characteristic somatic CNVs, suggesting shared molecular underpinnings with FA HNSCC. Heightened inflammation from genomic instability and transcriptional activation of retrotransposons contribute to tumorigenesis and increased invasiveness by the epithelial-to-mesenchymal transition. Due to heightened sensitivity to DNA crosslinking agents in patients with FA, platinum-based chemotherapy is generally avoided, which presents a significant hurdle for treatment and thereby leaves limited therapeutic options. Surgical management is the mainstay of therapy if possible, and targeted therapy has been increasingly studied in HNSCC in FA.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085117","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":"Prediction of Occult Cervical Lymph Node Metastasis in Bone-Invasive pT4a cN0 Oral Squamous Cell Carcinoma in Relation to Tumor Size: A Retrospective Observational Cohort Study.","authors":"Friedrich Mrosk, Victoria Vertic, Maximilian Richter, Erin Sprünken, Lukas Mödl, Jan Oliver Voss, Anna Sofroniou, Carsten Rendenbach, Max Heiland, Steffen Koerdt","doi":"10.3390/cancers17183044","DOIUrl":"10.3390/cancers17183044","url":null,"abstract":"<p><p><b>Objective:</b> The T classification of oral squamous cell carcinoma (OSCC) is linear according to the tumor size, excluding T4a by its criteria of invasion into adjacent structures, such as cortical bone. This may lead to the upstaging of otherwise small tumors. The objective was to analyze patients with OSCC and negative nodal staging to assess the impact of T-staging with tumor size on the incidence of occult cervical lymph node metastasis (CLNM) and regional neck failure. <b>Methods:</b> This retrospective cohort study included patients with OSCC and clinically negative necks (cN0), treated surgically between 2010 and 2024. All T4a OSCC classified due to bone invasion were additionally reclassified into T1-T3 based on size and depth of invasion according to the current staging manual. The primary endpoint of this study was the association between OSCC stratified by T-stage and tumor size as well as the presence of occult CLNM. <b>Results:</b> A total of 642 patients were included, with an overall occult CLNM rate of 20.2%. Bone invasion in T1-sized tumors was significantly associated with occult CLNM (OR 6.38, 95% CI: 1.48-27.42), whereas no such association was observed in T2 or T3 tumors (OR 0.80, 95% CI: 0.37-1.73; and OR 0.77, 95% CI: 0.37-1.62, respectively). Additionally, in T1-T2 tumors, bone invasion did not correlate with worse survival outcomes. <b>Conclusions:</b> Bone invasion was not significantly associated with occult CLNM in T2-3 sized OSCC, suggesting that the prognostic relevance is size-dependent. These findings question the uniform upstaging to T4a and support a more differentiated approach, potentially enabling neck management de-escalation in selected early-stage cases.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173462","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":"Defining Standard Data Reporting in Pelvic Exenterations for Non-Rectal Cancers: A Systematic Review of Current Data Reporting.","authors":"PelvEx Collaborative","doi":"10.3390/cancers17183049","DOIUrl":"10.3390/cancers17183049","url":null,"abstract":"<p><strong>Introduction: </strong>Pelvic exenteration (PEx) was first described in the 1940s as a palliative procedure in managing cervical cancer. Since then, advancements in perioperative care have transformed the options available to patients. This highly morbid procedure now offers a \"cure\" in a select cohort of patients with locally advanced and recurrent pelvic cancers. The large volume of literature in this field has resulted in a heterogeneity of data reporting, making comparative analysis extremely difficult. As such, we set out to examine the current literature and identify currently reported outcomes to guide development of a core information set (CIS) for data reporting for PEx in non-rectal cancers.</p><p><strong>Methods: </strong>A systematic review was carried out. Studies reporting on outcomes following PEx for advanced and recurrent gynecological, urological, and other non-rectal malignancies were included. Standardized outcomes were extracted and mapped to pre-determined domains.</p><p><strong>Results: </strong>Forty-four studies were found to meet our inclusion criteria. A total of 1735 data elements (DEs) were extracted verbatim, and these were assimilated into 111 standard DEs across nine domains. A wide range of reporting frequencies was observed, with the pathological domain containing the highest overall frequencies of DE reporting. Conversely, patient-reported and functional outcomes were noted to be the domain with the lowest frequency.</p><p><strong>Conclusions: </strong>This review highlights recent trends of increased reporting in the field of PEx and how this had invariably resulted in heterogeneous data reporting. We aim to guide the development of a CIS for reporting in non-rectal pelvic malignancies to help standardize future reporting.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173708","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":"Actinium-225/Bismuth-213 as Potential Leaders for Targeted Alpha Therapy: Current Supply, Application Barriers, and Future Prospects.","authors":"Mohamed F Nawar, Adli A Selim, Basma M Essa, Alaa F El-Daoushy, Mohamed M Swidan, Claudia G Chambers, Mohammed H Al Qahtani, Charles J Smith, Tamer M Sakr","doi":"10.3390/cancers17183055","DOIUrl":"10.3390/cancers17183055","url":null,"abstract":"<p><p>Alpha therapy (TAT) relies on combining alpha-emitting radionuclides with specific cell-targeting vectors to deliver a high payload of cytotoxic radiation capable of destroying tumor tissues. TAT efficacy comes from the tissue selectivity of the targeting vector, the high linear energy transfer (LET) of the radionuclide, and the short range of alpha particles in tissues. Recent research studies have been directed to evaluate TAT on a preclinical and clinical scale, including evaluating damage to tumor tissues with minimal toxic radiation effects on surrounding healthy tissues. This review highlights the use of Actinium-225/Bismuth-213 radionuclides as promising candidates for TAT. Herein, we begin with a discussion on the production and supply of [²²⁵Ac]Ac/[²¹³Bi]Bi followed by the formulation of [²²⁵Ac]Ac/[²¹³Bi]Bi-radiopharmaceuticals using different radiolabeling techniques. Finally, we have summarized the preclinical and clinical evaluation of these potential radiotheranostic agents.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173583","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":"Alterations in ¹³C and ¹⁵N Isotope Abundance as Potential Biomarkers for Tumor Biology and Risk Factors for Cervical Lymph Node Metastases in Oral Squamous Cell Carcinoma.","authors":"Katarzyna Bogusiak, Piotr Paneth, Józef Kobos, Marcin Kozakiewicz","doi":"10.3390/cancers17183047","DOIUrl":"10.3390/cancers17183047","url":null,"abstract":"<p><p><i>Background:</i> Cervical lymph node metastases are a major prognostic factor in patients with oral squamous cell carcinoma (OSCC). Despite advances in imaging, accurate preoperative prediction of nodal involvement remains a challenge. This study evaluated the utility of Isotope Ratio Mass Spectrometry (IRMS) in assessing the risk of lymph node metastases in patients with OSCC. We hypothesize that alterations in the abundance of ¹³C and ¹⁵N stable isotopes in OSCC tumor tissues reflect metabolic reprogramming associated with tumor progression and may correlate with cervical lymph node metastases. <i>Methods:</i> A prospective cohort of 61 patients with primary OSCC undergoing surgical treatment was analyzed. Tumor tissue samples were evaluated for the relative abundance of nitrogen-15 (¹⁵N) and carbon-13 (¹³C) isotopes using IRMS. Correlations between isotopic values and nodal metastases, as well as established clinicopathological risk factors, were assessed. <i>Results:</i> IRMS measurements of ¹³C and ¹⁵N abundance did not directly correlate with the presence of lymph node metastases but were associated with advanced tumor stages and negative prognostic features, such as angioinvasion/neuroinvasion. The median of the average nitrogen ¹⁵N content was higher in patients with more advanced clinical stages (11.89% in stage IV vs. 11.12% in stages I-III; <i>p</i> = 0.04‱), and the median δ¹³C was lower in stage IV compared to stages I-III (-22.40‱ vs. -22.88‱; <i>p</i> < 0.05). Patients with angioinvasion/neuroinvasion also had a lower median δ¹³C (-22.26‱ vs. -22.75‱; <i>p</i> < 0.05). These findings suggest that IRMS reflects metabolic changes in tumor biology rather than specifically predicting nodal metastases. Multivariate logistic regression identified age, gender, and clinical tumor stage as independent predictors of nodal involvement. <i>Conclusion:</i> IRMS-based isotopic profiling may reflect key metabolic alterations associated with OSCC progression. Although IRMS parameters of carbon ¹³C and nitrogen ¹⁵N were not independently predictive of lymph node status, they were associated with key adverse prognostic features, indicating their potential as adjunctive biomarkers that may complement traditional histopathological evaluation.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173735","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":"Chronic Liver Disease Associated Cholangiocarcinoma: Genomic Insights and Precision Therapeutic Strategies.","authors":"Kyoko Oura, Asahiro Morishita, Mai Nakahara, Tomoko Tadokoro, Koji Fujita, Joji Tani, Tsutomu Masaki, Hideki Kobara","doi":"10.3390/cancers17183052","DOIUrl":"10.3390/cancers17183052","url":null,"abstract":"<p><p><b>Background</b>: Cholangiocarcinoma (CCA) is a highly heterogeneous malignancy arising from the biliary epithelium, with an increasing incidence and poor prognosis worldwide. Recent advances in next-generation sequencing have revealed a variety of genomic alterations-such as FGFR2 fusions, IDH1 mutations, and ERBB2 amplification-that may serve as therapeutic targets. However, the influence of underlying etiologic factors, including chronic liver and biliary diseases, on the molecular landscape of CCA remains unclear. <b>Objective</b>: This review aimed to synthesize the current knowledge on the genomic and molecular alterations of CCA in the context of diverse etiologic factors, including hepatitis B virus, hepatitis C virus, primary sclerosing cholangitis (PSC), primary biliary cholangitis, metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-related liver disease (ALD), and liver fluke infection. <b>Main findings</b>: Certain backgrounds, such as PSC and liver fluke infection, are associated with distinct molecular signatures (e.g., TP53, SMAD4, KRAS, and ERBB2 alterations), whereas others, such as MASLD or ALD, show limited and inconsistent genomic data. Targetable alterations-including FGFR2 fusions, IDH1 mutations, and ERBB2 amplification-are heterogeneously distributed across etiologies and anatomical subtypes. Molecular targeted therapies such as FGFR and IDH1 inhibitors have shown clinical benefits in selected patients. <b>Conclusions</b>: A better understanding of how chronic liver and biliary diseases shape the genomic landscape of CCA will inform the development of personalized treatments, surveillance strategies, and preventive approaches. Large-scale etiology-stratified genomic studies integrating multiomics and real-world clinical data are urgently needed to advance precision oncology in CCA.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173907","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}