Cancers最新文献

{"title":"Clinical and Treatment-Related Factors Associated with Neutrophil Recovery After Bloodstream Infection in Acute Leukemia: A Competing-Risk Analysis.","authors":"Krzysztof Gawronski, Nadia Hussein, Piotr Rzepecki, Aneta Guzek","doi":"10.3390/cancers18193234","DOIUrl":"10.3390/cancers18193234","url":null,"abstract":"<p><strong>Background/objectives: </strong>Neutrophil recovery after bloodstream infection (BSI) in acute leukemia is clinically important, but evaluation is complicated by early death and recurrent infectious episodes. We assessed clinical, treatment-related, and microbiological factors associated with recovery while accounting for death as a competing event.</p><p><strong>Methods: </strong>This retrospective single-center cohort included 205 microbiologically documented BSI episodes in 101 adults with acute leukemia treated between 2020 and 2025. Neutrophil recovery was defined as an absolute neutrophil count >500/µL after BSI onset. The endpoint was evaluable in 186 episodes; 116 were followed by recovery and 70 by death before recovery. Recurrent episodes were retained and within-patient dependence was addressed by patient-level clustering in marginal Fine-Gray regression.</p><p><strong>Results: </strong>In the fully adjusted model (177 episodes, 93 patients), G-CSF use was associated with a higher cumulative incidence of recovery (sHR 3.17, 95% CI 1.40-7.18; <i>p</i> = 0.006), as was consolidation versus induction (sHR 2.50, 95% CI 1.44-4.33; <i>p</i> = 0.001). Clinically relevant antimicrobial resistance was not independently associated with recovery (sHR 0.80, 95% CI 0.38-1.68; <i>p</i> = 0.558). A literal-first-BSI sensitivity analysis supported the overall clinical pattern.</p><p><strong>Conclusions: </strong>Neutrophil recovery after BSI was associated primarily with treatment and clinical context, while the crude adverse association with antimicrobial resistance was substantially attenuated after adjustment. These observational associations, particularly those involving G-CSF, should not be interpreted causally.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191137","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":"A Totally Laparoscopic Transhiatal Approach for Esophageal Cancer During Mediastinoscopic Esophagectomy.","authors":"Hirotaka Konishi, Shutaro Sumiyoshi, Hiroyuki Inoue, Keiji Nishibeppu, Toshiyuki Kosuga, Yusuke Yamamoto, Ryo Morimura, Hitoshi Fujiwara, Atsushi Shiozaki","doi":"10.3390/cancers18193236","DOIUrl":"10.3390/cancers18193236","url":null,"abstract":"<p><strong>Background: </strong>Mediastinoscopic esophagectomy is a minimally invasive approach that avoids thoracotomy and single-lung ventilation. We previously performed this procedure using hand-assisted laparoscopic surgery (HALS) and recently established a totally laparoscopic transhiatal approach. This retrospective, non-randomized study reported laparoscopic technique and compared the feasibility and surgical outcomes of these approaches.</p><p><strong>Methods: </strong>We retrospectively reviewed 262 patients who underwent radical mediastinoscopic esophagectomy using left cervical and transhiatal approaches at the Kyoto Prefectural University of Medicine between January 2020 and June 2026. HALS was performed in 202 patients and laparoscopy in 60 patients. Surgical procedures and perioperative outcomes were compared between the groups.</p><p><strong>Results: </strong>Blood loss and total operative time did not differ significantly between the groups, although the transhiatal procedure tended to require a longer operative time with laparoscopy (<i>p</i> = 0.09). The approach used for middle mediastinal lymphadenectomy was similar between the two groups (43% vs. 35%, <i>p</i> = 0.28), and the overall number of dissected lymph nodes, excluding the upper mediastinal and cervical nodes, was comparable. However, significantly more abdominal lymph nodes were dissected with laparoscopy than with HALS (17.9 vs. 15.7, <i>p</i> = 0.04). Laparoscopic gastric mobilization and lymph node dissection were safely performed, with no significant differences in the rate of postoperative complications or curability.</p><p><strong>Conclusions: </strong>The totally laparoscopic transhiatal technique is a feasible and safe approach for mediastinoscopic esophagectomy, with surgical outcomes comparable to those of HALS and not inferior abdominal lymph node dissection. It may be particularly advantageous for cases requiring meticulous abdominal lymphadenectomy.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191197","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":"18β-Glycyrrhetinic Acid Exerts Subgroup-Specific Antitumor Activity and Enhances Radiosensitivity in Medulloblastoma.","authors":"Francesca Palone, Luca Marchetti, Marco Corso, Emiliano Fratini, Ilaria De Stefano, Ilaria Di Sarcina, Simonetta Pazzaglia, Mariateresa Mancuso","doi":"10.3390/cancers18193233","DOIUrl":"10.3390/cancers18193233","url":null,"abstract":"<p><strong>Background: </strong>Radiotherapy (RT) is a cornerstone of medulloblastoma (MB) treatment, but its efficacy may be limited by intrinsic or acquired radioresistance, while radiation-related late effects remain a major concern in pediatric patients. 18β-Glycyrrhetinic acid (18β-GA), a bioactive triterpenoid derived from <i>Glycyrrhiza glabra</i>, has shown antitumor activity in several malignancies. This study evaluated its antitumor and radiosensitizing effects in biologically distinct MB models.</p><p><strong>Methods: </strong>DAOY cells, used as an SHH-associated, TP53-mutant model, and D283 cells, commonly considered a Group 3/Group 4-associated model, were treated with 18β-GA (2.5-5 μM), γ-radiation (2-4 Gy), or their combination. Cell viability, clonogenic survival and migration were assessed. Apoptosis was evaluated by caspase-3/7 activity and cleaved caspase-3 expression. Modulation of AMPK/NF-κB and SHH signaling was examined by immunoblotting and RT-qPCR.</p><p><strong>Results: </strong>18β-GA reduced cell viability in a dose- and time-dependent manner and significantly reduced wound closure in DAOY cells and migratory capacity in D283 cells. D283 cells showed greater apoptotic sensitivity, accompanied by increased total and phosphorylated AMPK and reduced NF-κB p65 expression. In DAOY cells, 18β-GA reduced the expression of SHH-associated transcriptional markers, including GLI1, SOX2, CCND1, and MYC. Most importantly, 18β-GA significantly enhanced radiation response in both cell lines, producing greater reductions in viability and clonogenic survival than irradiation alone (<i>p</i> < 0.01). Combined treatment with 5 μM 18β-GA and 4 Gy reduced the surviving fraction to 0.013 in DAOY cells and approximately 0.01 in D283 cells (<i>p</i> < 0.001 versus radiation alone). This radiosensitizing effect was accompanied by increased caspase-3/7 activity and cleaved caspase-3 expression.</p><p><strong>Conclusions: </strong>18β-GA exerts antitumor activity in biologically distinct MB models through differential modulation of SHH and AMPK/NF-κB signaling, while converging on enhanced apoptotic susceptibility and a profound loss of clonogenic survival after irradiation. These findings provide a strong rationale for further preclinical evaluation of 18β-GA as a potential radiosensitizing adjuvant in MB.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191188","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":"The Dynamic Role of Liquid Biopsy in Patients with Non-Small Cell Lung Cancer Receiving Immune Checkpoint Inhibitors: Emerging Opportunities and Clinical Challenges.","authors":"Tancredi Didier Bazan Russo, Valerio Gristina, Francesco Pepe, Claudia Scimone, Giulia Busuito, Domenico Cozzolino, Claudia Sarracino, Giuseppina Ratto, Lorena Incorvaia, Nadia Barraco, Giuseppe Badalamenti, Antonio Galvano, Viviana Bazan, Antonio Russo, Giancarlo Troncone, Umberto Malapelle","doi":"10.3390/cancers18193240","DOIUrl":"10.3390/cancers18193240","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) have transformed the treatment of non-small-cell lung cancer (NSCLC), yet predicting durable benefit and detecting resistance remain major challenges. As immunotherapy expands across disease stages, minimally invasive tools are increasingly needed to monitor response and inform treatment personalization. Liquid biopsy enables serial assessment of circulating tumor DNA (ctDNA) and other blood-based biomarkers, complementing tissue analysis and imaging. This review critically synthesizes evidence across resectable, locally advanced, and metastatic NSCLC, integrating ctDNA dynamics with emerging multi-omics approaches. Its contribution is to distinguish the prognostic value of circulating biomarkers from evidence that using them to guide treatment improves patient outcomes, while identifying priorities for clinical translation. Across the reviewed studies, ctDNA clearance is associated with favorable outcomes, whereas persistent or rising ctDNA signals an increased risk of recurrence or progression, sometimes before radiological detection. Methylation, fragmentomics, plasma proteomics, and immune-cell profiling may provide complementary information on tumor-immune interactions. However, low tumor shedding, clonal hematopoiesis, assay variability, and unvalidated intervention thresholds limit routine use. The expansion of perioperative immunotherapy and emerging interest in biomarker-guided treatment adaptation make this synthesis timely. Prospective interventional trials are needed to determine whether liquid biopsy can safely guide treatment escalation, de-escalation, or discontinuation. By clarifying both the promise and the limitations of longitudinal monitoring, this review informs research aimed at detecting ineffective treatment earlier and reducing unnecessary treatment exposure while preserving cancer control.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191650","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":"From Infection to Oncology: AI-Assisted Drug Repurposing Uncovers Anti-Infective and Excipient-Class Compounds as PPAR-α-Linked Anticancer Agents.","authors":"Shoeb Ikhlas, Amani Alsharidah, Reem A Alkhodier, Sergio Senar, Mohamed Boudjelal","doi":"10.3390/cancers18193231","DOIUrl":"10.3390/cancers18193231","url":null,"abstract":"<p><p>Drug repurposing offers an efficient strategy to identify novel anticancer agents from marketed compounds. We screened a library of ~1400 approved drugs using a PPARE-PPAR-α luciferase reporter assay to uncover modulators of lipid metabolism that induce cancer cell death without direct binding to PPARα. This primary screen identified 224 compounds inhibiting reporter activity by >50%, of which 26 demonstrated ≥50% cytotoxicity in KAIMRC1 breast cancer and HCT116 colorectal cancer cells at 10 µM after 48 h incubation. AI-based DrTarget analysis classified these hits, with Group 1 comprising four previously unrecognized anticancer agents: antibiotics cefditoren pivoxil, tebipenem pivoxil, broxyquinoline, and cosmetic ingredient 1-hexadecanol. Dose-response studies across KAIMRC1, HCT116, and SW480 cells revealed IC₅₀ values as low as ~10 µM, comparable to daunorubicin, a well-known anti-cancer drug. Apoptosis profiling confirmed activation of intrinsic/extrinsic pathways via cytochrome c, SMAC/Diablo, TRAIL-R1/DR4, and phospho-p53 modulation. Based on these findings, we propose the repurposing of Broxyquinoline, 1-Hexadecanol, Cefditoren Pivoxil, and Tebipenem Pivoxil as potential anti-cancer drugs.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191109","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":"Radiation-Induced Contrast Enhancement After Proton Therapy for Paediatric Brain Tumours: Association with Variable Relative Biological Effectiveness and Linear Energy Transfer.","authors":"Julian Brack, Valon Gllareva, Bastian von Nettelbladt, Eva Meixner, Line Hoeltgen, Laila Koenig, Hanna Waldsperger, Katharina Kozyra, Habiba Sallem, Alexander Neuholz, Thomas Tessonnier, Andrea Mairani, Jürgen Debus, Klaus Herfarth, Semi B Harrabi","doi":"10.3390/cancers18193243","DOIUrl":"10.3390/cancers18193243","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Proton therapy is widely used in paediatric neuro-oncology because of its favourable dose distribution and reduced exposure to radiation of healthy tissue. Nevertheless, current knowledge regarding radiation-induced contrast enhancements (RICE) is largely derived from adult proton therapy cohorts, while evidence in paediatric patients remains limited and the underlying biological mechanisms are still incompletely understood. This study investigated the incidence of RICE in paediatric patients with low-grade glioma (LGG) and ependymoma and evaluated potential associations with linear energy transfer (LET) and variable relative biological effectiveness (RBE)-weighted dose distributions. <b>Methods</b>: In this retrospective single-centre study, paediatric patients with LGG or ependymoma were identified from a prospectively maintained institutional registry patients treated with proton therapy at the Heidelberg Ion-Beam Therapy Centre (HIT) between 2010 and 2024. Follow-up magnetic resonance imaging examinations were systematically reviewed for RICE. Lesions were contoured in RayStation and assessed dosimetrically using a fixed RBE of 1.1 and three variable RBE models. LET-weighted dose metrics and Dose_(RBE) × LET products were compared between RICE regions and planning target volumes (PTVs). Overall survival and progression-free survival were estimated using Kaplan-Meier method. <b>Results</b>: Seventy-six patients met the inclusion criteria, including 33 patients with LGG and 43 with ependymoma. A total of 724 follow-up magnetic resonance imaging examinations were reviewed. RICE occurred in six patients (7.9%), exclusively in the ependymoma subgroup (14.0%). Higher prescribed radiation dose was significantly associated with RICE occurrence (<i>p</i> = 0.031). Across all variable RBE models, biologically weighted dose estimates and Dose_(RBE) × LET products were consistently elevated within RICE regions compared with corresponding PTV regions, particularly at low- and intermediate-dose levels. Five-year overall survival rates were 91.7% for LGG and 86.6% for ependymoma, while corresponding progression-free survival rates were 84.4% and 69.3%, respectively. <b>Conclusions</b>: Variable RBE models identified biologically relevant dose heterogeneities within RICE regions that were not adequately captured by the conventional fixed RBE approach. These findings suggest that LET-associated biological dose escalation may contribute to radiation-related brain tissue changes after proton therapy and support further investigation and prospective validation of LET- and RBE-informed normal-tissue risk assessment in paediatric neuro-oncology.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191596","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":"Recent Developments in Studies on the Relation Between Endometriosis and Ovarian Cancer: Phenotype-Specific Risk, Molecular Convergence and Clinical Risk Stratification.","authors":"Klaudia Gutowska, Aleksandra Urban, Cezary Wojtyła, Sławomir Ławicki, Piotr Laudański","doi":"10.3390/cancers18193241","DOIUrl":"10.3390/cancers18193241","url":null,"abstract":"<p><p><b>Background/Objectives</b>: We aim to synthesize recent clinical and translational evidence on the relationship between endometriosis and ovarian cancer, with emphasis on publications from 2024 to 2026 and on clinically conservative risk stratification. <b>Materials and Methods</b>: This state-of-the-art narrative review prioritizes major peer-reviewed publications from July 2024 to June 2026. Older landmark publications were used only where necessary to contextualize recent findings. <b>Results</b>: Recent evidence supports a selective, phenotype-dependent association instead of a generalized malignant potential of endometriosis. The strongest and most reproducible signal concerns epithelial ovarian cancer, especially clear-cell and endometrioid ovarian carcinoma, with the highest relative risks reported for ovarian endometrioma and/or deep endometriosis. The ENDOCANCER meta-analysis found increased ovarian cancer risk across odds ratio, hazard ratio and standardized incidence ratio estimates but confirmed low absolute incidence and substantial heterogeneity. Contemporary reviews, including Leone Roberti Maggiore et al. and Bogani et al., emphasize low absolute lifetime risk and the absence of evidence supporting universal oncologic surveillance. Newer clinicopathological studies distinguish endometriosis-correlated tumors supported by transitional lesions indicative of malignant transformation from incidental coexistence. Molecular data support biological plausibility through <i>ARID1A</i>, <i>PIK3CA</i>, <i>KRAS</i>, <i>PTEN</i>, mismatch repair deficiency, <i>POLE</i>-mutated disease and p53-abnormal phenotypes, but these markers are not ready for routine prediction in endometriosis care. <b>Conclusions</b>: The immediate clinical implication is individualized risk assessment in place of routine cancer screening or prophylactic surgery based solely on the increased cancer risk associated with endometriosis. Counseling should integrate endometriosis phenotype, age, menopausal status, lesion dynamics, imaging atypia, hereditary cancer risk, reproductive goals and surgical consequences.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191185","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":"Long-Term Outcomes of a Multidisciplinary Treatment Strategy Using Neoadjuvant Gemcitabine Plus S-1 Based on Anatomical Resectability Classification and Lymph Node Status in Patients with Perihilar Cholangiocarcinoma.","authors":"Naohisa Kuriyama, Shugo Mizuno, Yuki Segi, Haruna Komatusbara, Kazuyuki Gyoten, Takahiro Ito, Aoi Hayasaki, Takehiro Fujii, Yusuke Iizawa, Yasuhiro Murata, Akihiro Tanemura, Masashi Kishiwada","doi":"10.3390/cancers18193238","DOIUrl":"10.3390/cancers18193238","url":null,"abstract":"<p><p><b>Objectives:</b> The long-term impact of neoadjuvant chemotherapy (NAC) based on anatomical resectability for perihilar cholangiocarcinoma (PHC) remains unclear. We evaluated the mature long-term outcomes of our multidisciplinary treatment strategy based on anatomical resectability classification and regional lymph node (LN) status using gemcitabine plus S-1 (NAC-GS). <b>Methods:</b> Between September 2010 and August 2021, 110 consecutive PHC patients were classified as resectable (R; <i>n</i> = 47), borderline resectable (BR; <i>n</i> = 38), or unresectable locally advanced (UR-LA; <i>n</i> = 25) according to our anatomical resectability classification. NAC-GS was administered to patients with clinically positive LN metastasis and to BR and UR-LA patients. Long-term overall survival (OS), recurrence-free survival (RFS), and prognostic factors were evaluated. <b>Results:</b> NAC-GS was administered to 72 patients (65.5%). Curative-intent resection was achieved in 40 (85.1%), 25 (65.8%), and 6 (24.0%) patients in the R, BR, and UR-LA groups, respectively. In the overall cohort, anatomical resectability significantly stratified OS (<i>p</i> = 0.032). However, among patients who underwent curative-intent resection, OS and RFS were comparable across the three resectability groups. Those receiving NAC-GS showed favorable long-term survival despite having more advanced disease characteristics; however, this comparison was limited to selected patients who ultimately proceeded to surgery. Multivariable analysis identified preoperative serum carcinoembryonic antigen ≥5.5 ng/mL (HR: 3.174, <i>p</i> = 0.003), non-adjuvant therapy (HR: 2.222, <i>p</i> = 0.023) and pathological T4 (HR: 2.397, <i>p</i> = 0.037) as independent predictors of poor survival. <b>Conclusions:</b> Anatomical resectability was associated with long-term prognosis and the likelihood of achieving curative-intent resection. Selected patients who ultimately underwent curative-intent resection after NAC-GS showed favorable long-term outcomes; however, these findings do not establish a survival benefit of NAC-GS over upfront surgery. Prospective multi-institutional validation is warranted.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191460","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":"Targeting SERPINB5 and MSLN for Pancreatic Cancer Therapy.","authors":"Jinghui Sun, Lingling Liu, Rhyston Broadhurst, David Wang, Anand Mehta, Denis C Guttridge, Leonardo M R Ferreira, Haizhen Wang, Xueliang Gao","doi":"10.3390/cancers18193242","DOIUrl":"10.3390/cancers18193242","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Pancreatic cancer (PC) is a leading cause of cancer-related death in the United States and lacks efficient therapeutic options. Serine peptidase inhibitor, clade B, member 5 (SERPINB5) is non-inhibitory toward serine proteases, yet it has diverse biological functions, including regulating cell migration, cell death, gene expression, and stress responses. Mesothelin (MSLN) is a tumor-associated antigen that is broadly overexpressed on various malignant tumor cells and plays a crucial role in promoting proliferation, invasion, and metastasis. <b>Methods</b>: We integrated public database analyses, cell-line screening, gene knockdown and overexpression, immunoblotting, cell viability and apoptosis assays, flow cytometry, chromatin immunoprecipitation paired with quantitative PCR (ChIP-qPCR), and chimeric antigen receptor (CAR) T-cell therapy to investigate SERPINB5 and MSLN functions, developing a novel and effective therapeutic strategy for patients with pancreatic cancer. <b>Results</b>: Both SERPINB5 and MSLN are highly expressed and negatively associated with the overall survival of PC patients. Our mechanistic study suggests that SERPINB5 negatively regulates the mitochondrial protein dehydrogenase/reductase 2 (DHRS2) to promote PC cell survival; consequently, SERPINB5 depletion induces PC cell apoptosis. Of note, SERPINB5 depletion increases MSLN transcription by enhancing c-Myc binding to the MSLN promoter region, which in turn suppresses the mitochondrial protein DHRS2 and leads to resistance to apoptosis in PC cells. Our genetic ablation study shows that SERPINB5 and MSLN are critical for PC cell survival, and that depleting both proteins synergistically induces PC cell apoptosis. Gemcitabine (GEM) is a standard chemotherapy drug for PC treatment. Our study shows that SERPINB5-high PC cells display greater sensitivity to GEM than SERPINB5-low PC cells. GEM treatment increases mitochondrial DHRS2 protein expression, similar to the effect of SERPINB5 knockdown, whereas upregulated MSLN confers apoptotic resistance by decreasing DHRS2 levels. <b>Conclusions</b>: Our in vitro study demonstrates that sequential treatment with GEM followed by anti-MSLN chimeric antigen receptor (CAR)-T cells is an effective and promising strategy for patients with pancreatic cancer. Future studies using mouse models may validate the efficacy of this sequential treatment strategy in vivo.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191538","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":"Multi-Omics and Liquid Biopsy Integration for Precision Stratification of Breast Cancer.","authors":"Dheeraj Sharma, Shriyansh Srivastava, Sathvik Belagodu Sridhar, Javedh Shareef, Rakesh Sahu, Roja Rani Budha, Mohd Tariq, Mohammad Amjad Kamal","doi":"10.3390/cancers18193235","DOIUrl":"10.3390/cancers18193235","url":null,"abstract":"<p><p>Breast cancer is a biologically heterogeneous disease that requires accurate diagnosis, risk stratification, treatment selection and longitudinal assessment. Conventional imaging and tissue biopsy remain the mainstays of clinical management. However, tissue sampling represents a specific anatomical site and time point, and may not reflect the molecular heterogeneity or evolution of disease. Liquid biopsy offers a minimally invasive complementary approach, analyzing circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and extracellular vesicles. Applications include molecular characterization, treatment-response assessment, resistance detection and minimal residual disease (MRD) evaluation, which are under investigation or in clinical use. Gene-expression profiles, mutational alterations and epigenetic marks can generate molecular signatures that offer further support for tumor classification and risk stratification, and have demonstrated clinical value in specific breast cancer populations. Advances in next-generation sequencing, digital PCR, proteomic analysis, and artificial intelligence have expanded the analytical capacity for detection and interpretation of circulating and tissue-derived biomarkers. However, biological heterogeneity, low abundance of circulating biomarkers, pre-analytical and analytical variability, standardization of assays and limited prospective evidence for some applications are still major barriers to clinical translation. In this review, we discuss the biological basis, detection technologies, clinical applications and limitations of liquid biopsies and molecular signatures in breast cancer, highlighting multi-omics integration and computational approaches. It distinguishes between promising analytical biomarkers and clinically validated applications and highlights the evidence and methodological needs for wider implementation in precision breast cancer care.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191220","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}