Cancers最新文献

{"title":"Nerve-Sparing Robotic-Assisted Radical Prostatectomy Based on the Absence of Prostate Imaging-Reporting and Data System ≥3 or Biopsy Gleason Pattern ≥4 in the Peripheral Zone.","authors":"Yoichiro Tohi, Hiroyuki Tsunemori, Kengo Fujiwara, Takuma Kato, Kana Kohashiguchi, Asuka Kaji, Satoshi Harada, Yohei Abe, Hirohito Naito, Homare Okazoe, Rikiya Taoka, Nobufumi Ueda, Mikio Sugimoto","doi":"10.3390/cancers17060962","DOIUrl":"10.3390/cancers17060962","url":null,"abstract":"<p><p><b>Background/Objectives</b>: The objective of this study was to evaluate the oncological outcomes and safety of nerve-sparing (NS) robot-assisted radical prostatectomy (RARP) when applied without Prostate Imaging-Reporting and Data System (PI-RADS) ≥3 lesions or Gleason pattern ≥4 on biopsy in the peripheral zone (PZ). <b>Methods</b>: We retrospectively analyzed 208 patients who underwent RARP between August 2017 and December 2022, excluding those who had received preoperative hormonal therapy. After NS status stratification and patient characteristic adjustment using propensity score matching (PSM), positive resection margin (RM) rates and prostate-specific antigen (PSA) recurrence-free survival were compared. Urinary and sexual quality of life (QOL) were assessed using the Expanded Prostate Cancer Index Composite, along with predictive factors associated with positive RM and RM locations in the NS group. <b>Results</b>: NS was performed in 68.6% (<i>n</i> = 129) patients. After PSM, there were no significant differences in RM positivity (<i>p</i> = 0.811) or PSA recurrence-free survival (Log-rank <i>p</i> = 0.79), regardless of NS status. There was no difference in sexual function between groups, but urinary QOL was significantly better in the NS group from the third month onward. In the NS group, RM positivity was 27.9% (n = 36), and diagnostic PSA (odds ratio [OR], 1.110, <i>p</i> = 0.038) and clinical T stage (OR, 1.400, <i>p</i> = 0.038) were predictive factors. The RM positivity rate on the NS side was 10.8%. <b>Conclusions</b>: NS, based on the absence of PI-RADS ≥3 lesions or Gleason pattern ≥4 in PZ, did not increase RM positivity rate and increased early urinary QOL.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728882","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":"Assessing Serum Pepsinogen and <i>Helicobacter pylori</i> Tests for Detecting Diffuse-Type Gastric Cancer: Insights from a Large-Scale and Propensity-Score-Matched Study in Republic of Korea.","authors":"Seon Hee Lim, Nayoung Kim, Yonghoon Choi, Ji Min Choi, Yoo Min Han, Min-Sun Kwak, Goh Eun Chung, Ji Yeon Seo, Sung Min Baek, Hyuk Yoon, Young Soo Park, Dong Ho Lee","doi":"10.3390/cancers17060955","DOIUrl":"10.3390/cancers17060955","url":null,"abstract":"<p><p>The incidence of cancer and its associated mortality have increased over the past several decades [...].</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728808","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":"Humanized Anti-MUC16 Antibody-Conjugated Contrast Agents for Magnetic Resonance Imaging of Pancreatic Cancer.","authors":"Jayasindu Mathiyazhagan, Christabelle Rajesh, Satish Sagar, Thomas C Caffrey, Ying Huang, Aaron M Mohs, Benjamin J Swanson, Michael A Hollingsworth, Cory L Brooks, Prakash Radhakrishnan","doi":"10.3390/cancers17060957","DOIUrl":"10.3390/cancers17060957","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Pancreatic ductal adenocarcinoma (PDAC) is diagnosed at a late stage with distant metastasis in an overwhelming 50% of cases, and the prognosis is poor. Treating this extremely aggressive disease with standard-of-care therapies has led to modest benefits in overall survival, mainly due to a lack of targeted early treatment modalities, as early detection has not yet been possible. Mucin-16 (MUC16) is a glycoprotein overexpressed in more than 60% of patients with PDAC and is a tumor-specific biomarker. <b>Methods:</b> In this study, a magnetic resonance imaging (MRI) probe to facilitate the detection of early and late lesions of PDAC is developed by conjugating a MUC16-targeted humanized antibody (huAR9.6) with gadolinium. <b>Results:</b> In preclinical mouse models, this MUC16-targeted MRI probe demonstrates effective contrast enhancement in early lesions of PDAC in the subcutaneous setting and allows for the detection of late-stage pancreatic cancer tumors in an orthotopic model. The probe did not induce any toxicity in vital organs at the administered doses. <b>Conclusions:</b> This study establishes that synthesizing a MUC16-targeted MRI probe is feasible and allows for the better high-resolution contrast enhancement of MUC16+ PDAC lesions to facilitate detection and possibly better treatment strategies.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729004","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":"ASPH Is a Metastatic Factor and Therapeutic Target in Chondrosarcoma.","authors":"Xiaojuan Sun, Jesse Hart, Ross Taliano, Janine Molino, Joseph H Schwab, Sjoerd Nota, Katsuya Nagaoka, Songhua Zhang, Mark Olsen, Rolf Carlson, Jack Wands, Richard M Terek","doi":"10.3390/cancers17060951","DOIUrl":"10.3390/cancers17060951","url":null,"abstract":"<p><p><b>Background:</b> Chondrosarcoma (CS) is a highly aggressive primary malignant bone tumor for which there are no effective systemic treatments. We assessed aspartate β-hydroxylase (ASPH) as a potential treatment target. ASPH is a transforming cell surface receptor, but its role in chondrosarcoma has not been evaluated. Our goals were to analyze the expression of ASPH in conventional chondrosarcoma, evaluate its utility as a biomarker, and determine if ASPH inhibition diminishes tumor progression in a preclinical model. <b>Methods:</b> An annotated tissue microarray was constructed with conventional chondrosarcoma tissues. ASPH expression was quantified with immunohistochemistry. A small molecule inhibitor (SMI) designed to inhibit ASPH activity was evaluated in two CS cell lines with intact ASPH expression and after knockout. Cell viability, invasion, and matrix metalloproteinase (MMP) expression were measured. A mouse xenograft chondrosarcoma model was used to evaluate the effect of the SMI on tumor growth, MMP activity in tumors, and lung metastatic burden. <b>Results:</b> Higher ASPH scores were associated with a greater risk of death and metastasis. The SMI decreased CS cell proliferation, invasion, and secretion of MMPs in vitro, and the effects were lost after ASPH knockout. In vivo, systemic administration of the SMI decreased tumor growth, MMP activity and content in xenograft tumors, and lung metastatic burden. <b>Conclusions:</b> These data validate ASPH as a biomarker in CS and as a factor in the metastatic phenotype. Systemic treatment with an SMI directed against ASPH inhibits tumor progression in a preclinical model, suggesting that ASPH-targeted therapy may be a new treatment strategy for chondrosarcoma expressing ASPH.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728773","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":"Prostate-Specific Antigen Decline Rate in the First Month Is a Timely Predictive Factor for Biochemical Recurrence After Robot-Assisted Radical Prostatectomy.","authors":"Pengfeng Gong, Hisamitsu Ide, Yan Lu, Masayoshi Nagata, Tomoki Kimura, Toshiyuki China, Ippei Hiramatsu, Takuro Kobayashi, Yoshihiro Ikehata, Jun Zhou, Shigeo Horie","doi":"10.3390/cancers17060961","DOIUrl":"10.3390/cancers17060961","url":null,"abstract":"<p><p><b>Objectives</b>: We attempt to assess whether prostate-specific antigen decline rate in the first month (PSADR1M = postoperative PSA in the first month/initial PSA) acts as a predictor for biochemical recurrence (BCR) and to evaluate other preoperative and postoperative variables that may predict BCR following robot-assisted laparoscopic prostatectomy (RARP). <b>Method</b>: Based on the D'Amico risk classification system, 777 patients who underwent RARP for localized prostate cancer were classified into a low/intermediate-risk group (<i>n</i> = 435) and a high-risk group (<i>n</i> = 342). The predictors of BCR were identified by univariate and multivariate logistic regression analyses. The area under the curve (AUC) and optimal cutoff values of PSADR1M were determined by receiver operating characteristic (ROC) analysis. Kaplan-Meier curves for biochemical recurrence-free survival (BRFS) rates were stratified by optimal cutoff values of PSADR1M. <b>Results</b>: Effective predictors of BCR in the entire cohort included pT3 (<i>p</i> < 0.001), pathological Grade Group (pGG3, pGG4+5) compared to pGG1+2 (<i>p</i> < 0.001, <i>p</i> = 0.017), positive surgical margins (PSM) (<i>p</i> < 0.001), seminal vesicle invasion (SVI) (<i>p</i> = 0.006), and PSADR1M ≥ 0.62% (<i>p</i> < 0.001). ROC analysis showed that PSADR1M as a predictor for BCR had an AUC of 0.762 for the whole cohort, and 0.821 for the high-risk group, respectively. The optimal cutoff values of PSADR1M were 0.62% in the whole cohort, and 0.68% in high-risk group. <b>Conclusions</b>: As an effective predictor of BCR, PSADR1M can assess the tumor status of prostate cancer patients intuitively and effectively after RARP, especially in the high-risk group.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728812","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 Uptake Period on ¹⁸F-DCFPyL-PSMA PET/CT Maximum Standardised Uptake Value.","authors":"Anthony-Joe Nassour, Anika Jain, Hadia Khanani, Nicholas Hui, Nadine J Thompson, Brian Sorensen, Sris Baskaranathan, Philip Bergersen, Venu Chalasani, Thomas Dean, Max Dias, Michael Wines, James Symons, Lisa Tarlinton, Henry Woo","doi":"10.3390/cancers17060960","DOIUrl":"10.3390/cancers17060960","url":null,"abstract":"<p><strong>Background: </strong>The maximum standardised uptake value (SUV_max) can potentially be affected by the uptake period during PSMA PET imaging. The optimal image acquisition period for 2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (¹⁸F-DCFPyL)PSMA PET/CT is yet to be established. This study aims to evaluate the effect of the uptake period on the SUV_max in diagnosing localised, clinically significant prostate cancer using ¹⁸F-DCFPyL-PSMA PET/CT.</p><p><strong>Methods: </strong>Sixty biopsy-naive men with one or more PI-RADS 4 or 5 lesions of at least 10 mm on multiparametric MRI (mpMRI) were enrolled to undergo ¹⁸F-DCFPyL-PSMA PET/CT. SUV_max was prospectively measured following an uptake period of 60, 90 and 120 min post injection of ¹⁸F-DCFPyL-PSMA radiotracer. Concordance with biopsy results or final histopathology was recorded.</p><p><strong>Results: </strong>Mean absolute differences in SUV_max at 60 vs. 90, 60 vs. 120, and 90 vs. 120 min uptake periods were 3.23 (SD 4.76), 4.53 (SD 7.33), and 3.24 (SD 4.56), respectively. This represents a statistically significant systematic increase in SUV_max (<i>p</i>-value < 0.001) with increasing uptake period. The interval between the uptake period of 60 vs. 120 min represented the largest SUV_max change of 29.98%.</p><p><strong>Conclusions: </strong>The SUV_max is a dynamic variable significantly affected by uptake period. Our study supports image acquisition at 120 min following injection of ¹⁸F-DCFPyL radiotracer. Further studies are needed to determine if this acquisition period can be applied to other Fluorine-18 based PSMA radiotracers.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728774","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":"Association Between Suicidal Ideation and Cancer Screening Uptake: Results from Middle-Aged and Older Adults in Korea.","authors":"Seong-Uk Baek, Jin-Ha Yoon","doi":"10.3390/cancers17060956","DOIUrl":"10.3390/cancers17060956","url":null,"abstract":"<p><strong>Background: </strong>Compliance with cancer screening guidelines is crucial for the early diagnosis and prevention of cancer. We explored the association of suicidal ideation with participation in cancer screening programs.</p><p><strong>Methods: </strong>This cross-sectional analysis included a nationwide sample consisting of 22,554 Korean adults (9667 men and 12,887 women). Suicidal ideation in the past year was self-reported (yes or no). Participation in gastric, colorectal, cervical, and breast cancer screening within the past 2 years was assessed. Logistic regression models were employed to determine the association of suicidal ideation with participation in each cancer screening test. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated.</p><p><strong>Results: </strong>Among men, the participation rates in gastric and colorectal cancer screening were 47.6% and 39.7%, respectively. Among women, the participation rates in gastric, colorectal, cervical, and breast cancer screening were 47.1%, 34.8%, 44.3%, and 50.8%, respectively. In the male sample, suicidal ideation was associated with reduced participation in gastric cancer screening (OR: 0.83, 95% CI: 0.69-0.99) and colorectal cancer screening (OR: 0.82, 95% CI: 0.67-1.00). Similarly, in the female sample, suicidal ideation was inversely associated with participation in gastric (OR: 0.74, 95% CI: 0.67-0.82), colorectal (OR: 0.71, 95% CI: 0.62-0.81), cervical (OR: 0.75, 95% CI: 0.68-0.84), and breast cancer screening (OR: 0.76, 95% CI: 0.68-0.84).</p><p><strong>Conclusions: </strong>This study suggests that individuals with suicidal ideation demonstrated reduced participation in cancer screening tests. This study highlights the need for targeted support to improve access to cancer screening programs for individuals with mental health problems.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728826","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":"Opportunities and Challenges in Antibody-Drug Conjugates for Cancer Therapy: A New Era for Cancer Treatment.","authors":"Idil Buyukgolcigezli, Ates Kutay Tenekeci, Ibrahim Halil Sahin","doi":"10.3390/cancers17060958","DOIUrl":"10.3390/cancers17060958","url":null,"abstract":"<p><p>The antibody, linker, and payload moieties all play a significant role in giving the ADC its unique therapeutic potential. The antibody subclass employed in ADCs is determined based on relative individual receptor affinities and pharmacokinetics. Meanwhile, the linker used in an ADC can either be cleavable or non-cleavable. ADC therapy comprises antibody-dependent mechanisms in addition to the direct cytotoxic effects of the payload. These include antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and antibody-dependent cellular phagocytosis, as well as the \"bystander effect\", which refers to the diffusion of a portion of the cytotoxic molecules out of the target cell, exerting its cytotoxic effect on the adjacent cells. Target antigens of ADCs are expected to be expressed on the membranes of the cancer cells facing the external matrix, although new approaches utilize antigens regarding tumor-associated cells, the tumor microenvironment, or the tumor vasculature. These target antigens of ADCs not only determine the efficacy of these agents but also impact the off-targets and related adverse effects. The majority of ADC-related toxicities are associated with off-targets. The proposed mechanisms of ADC resistance include disrupted intracellular drug trafficking, dysfunctional lysosomal processing, and the efflux of the cytotoxic molecule via ATP-binding cassette (ABC) transporters. The latter mechanism is especially prominent for multi-drug-resistant tumors. An important limitation of ADCs is the penetration of the conjugate into the tumor microenvironment and their delivery to target cancer cells. Cancerous tissues' vascular profile and the steric \"binding site barrier\" formed around the peripheral vessels of tumors stand as potential challenges of ADC therapy for solid tumors. As research efforts focus on reducing toxicities, overcoming resistance, and improving pharmacokinetics, ADC options for cancer therapy are expected to continue to diversify, including standalone approaches and combination therapies.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728891","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":"Historic p87 Is Diagnostic for Lung Cancer Preceding Clinical Presentation by at Least 4 Years.","authors":"Martin Tobi, Daniel Ezekwudo, Yosef Y Tobi, Xiaoqing Zhao, Fadi Antaki, MaryAnn Rambus, Edi Levi, Harvinder Talwar, Benita McVicker","doi":"10.3390/cancers17060952","DOIUrl":"10.3390/cancers17060952","url":null,"abstract":"<p><p>Lung cancer remains the most common cancer worldwide, with a limited prognosis despite personalized treatment regimens. Low-dose computed tomography (CT) scanning as a means of early diagnosis has been disappointing due to the high false positive rate. Other non-invasive means of testing need to be developed that offer both timely diagnosis and predict prognosis. <b>Methods</b>: In the course of stool testing in large-scale testing of 2922 patients at increased risk of CRC, we were able to ascertain 112 patients documented to have prospectively been diagnosed with lung cancer. Stool and colonic effluents were tested for p87 with anti-adenoma antibody (Adnab-9) reactivity by ELISA and Western blot. Survival data were obtained where available. <b>Results</b>: Of 112 cancers, approximately 27.6% were squamous (SSC), 17.9% were adenocarcinoma, 8% were small, 6.25% were large cell, 3.57% were designated non-small cell cancer (NSCLC), 0.89% were indeterminate, 0.89% were lepidic spread, 3.57% had metastasis, and in 31.25%, data were unavailable. In total, 49.1% of the lung cancer patients had fecal Adnab-9 testing. Overall, 60% had positive testing compared to 38%, which was significant (OR2.19 [1.06-4.53]; <i>p</i> = 0.045). Cancers with higher lethality were less likely to test positive (approximately 8.5% each for both small and large cell lung cancers) and higher, with 56% for SCC and 25% for adenocarcinoma (0% NSCLC). In the larger groups, overall survival was worse in those testing positive: 474 testing positives versus 844 days in SCC and 54 testing positive versus 749 days in adenocarcinoma patients. Most importantly, the time from a positive test to the clinical diagnosis ranged from 2.72 years for small cell, 3.13 for adenocarcinoma, 5.07 for NSCLC, 6.07 for SSC, and 6.24 for large cell cancer. In excluded cases where cancer in the lung was believed to be metastatic, 83.3% of cancers were positive. <b>Conclusions</b>: At a projected real-world sensitivity of 0.60 and specificity of 0.60, and the ability to predate diagnosis by up to 4.7 years overall, this test could help direct lung cancer screening. In addition, the Adnab-9 testing selectively detects worse tumor types (87.5%) and those with worse prognoses amongst the more common, favorable phenotypes, thus making early diagnosis possible in those patients who stand to benefit most from this strategy. Metastatic lung cancer, also detected by the test, should be identified by the follow-up imaging studies and, therefore, would not be considered to be a major pitfall.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729003","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":"Transcriptome Analysis of Canine Histiocytic Sarcoma Tumors and Cell Lines Reveals Multiple Targets for Therapy.","authors":"Alexander I Engleberg, Ya-Ting Yang, Peter Z Schall, Marilia Takada, Tuddow Thaiwong-Nebelung, Jacquelyn M Evans, Elaine A Ostrander, Vilma Yuzbasiyan-Gurkan","doi":"10.3390/cancers17060954","DOIUrl":"10.3390/cancers17060954","url":null,"abstract":"<p><p><b>Background</b>: Histiocytic sarcoma (HS) is a highly aggressive malignancy characterized by the excessive proliferation of histiocytes in dogs and humans. A subset of dog breeds, including the Bernese Mountain Dog (BMD), show a remarkably high prevalence of HS. Previous work by us and others has identified somatic driver mutations of HS in the <i>PTPN11</i> and <i>KRAS</i> genes that activate the MAPK pathway in about 60% of canine HS. However, no somatic driver mutations have been identified in the remaining 40%. <b>Objectives</b>: Our goals are to study HS in BMDs to gain insight into the molecular pathogenesis of the disease, and identify rational approaches to therapy. Methods: Here, we report our whole transcriptome analysis of 18 well-characterized BMD HS tumor tissues, as well as three HS cell lines. <b>Results</b>: Our analysis reveals the significant upregulation of molecular pathways involving the <i>FOXM1</i>, <i>AURKB</i>, <i>PLK1</i>, and <i>E2F</i> genes, in HS as well as hemophagocytic HS, providing new information regarding pathways that may be targeted with inhibitors. In addition, we document the expression of multiple checkpoint genes, suggesting the option of treatment with small-molecule inhibitors together with checkpoint inhibitors. Further, we show that the transcriptomes of three canine HS cell lines mirror those of canine patient tumors, further highlighting their potential use in drug discovery and efficacy studies. Finally, we demonstrate, for the first time, that aurora kinase inhibitors are effective in curtailing the growth of HS cells in vitro and show synergism with MAPK inhibition. <b>Conclusions</b>: This study provides the most detailed analysis of the canine HS transcriptome to date, highlighting key pathways in its pathogenesis and suggesting new avenues for both single and combination treatment strategies, which may be pertinent to the treatment of human HS.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728733","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}