Neoplasia最新文献

{"title":"Pancreatic cancer cells infiltrate nerves through TGFbeta1-driven perineural epithelial-to-mesenchymal-like transdifferentiation","authors":"Theresa Krauss ,&nbsp;Ibrahim Halil Gürcinar ,&nbsp;Ulrike Bourquain ,&nbsp;Maren Hieber ,&nbsp;Evelyn N. Krohmer ,&nbsp;Nan Wu ,&nbsp;Sergey Tokalov ,&nbsp;Rüdiger Goess ,&nbsp;Carmen Mota Reyes ,&nbsp;Dieter Saur ,&nbsp;Helmut Friess ,&nbsp;Güralp O. Ceyhan ,&nbsp;Ihsan Ekin Demir ,&nbsp;Okan Safak","doi":"10.1016/j.neo.2025.101126","DOIUrl":"10.1016/j.neo.2025.101126","url":null,"abstract":"<div><div>Neural invasion is a prognostic hallmark of pancreatic ductal adenocarcinoma (PDAC), yet the underlying mechanisms behind the disruption of perineural barriers and access of cancer cells into intrapancreatic nerves remain poorly understood. This study aimed to investigate the role of epithelial-mesenchymal transformation (EMT) in perineural epithelial cells during neural invasion.Histopathological analysis of human and murine primary tumors using perineurium-specific GLUT1 antibody revealed a reduction in perineural integrity, which positively correlated with the extent of neural invasion in human PDAC cases. Human pancreatic cancer cell lines were found to secrete TGFbeta1, which induced EMT of perineural epithelial cells, characterized by the loss of epithelial markers (CK19-9) and the acquisition of mesenchymal markers (alphaSMA, N-Cadherin). Additionally, these transitioning perineural epithelial cells demonstrated increased matrix-degrading capabilities through the upregulation of matrix-metalloproteases 3 and 9 via SMAD2. In an autochthonous mouse model with elevated endogenous TGFbeta1 levels in addition to oncogenic Kras activation (<em>Ptf1a^Cre/+, LSL-Kras^G12D/+, LSL-R26^Tgfβ/+</em>), decreased perineural integrity could be reproduced <em>in vivo</em>.Collectively, these findings underscore the role played by TGFbeta1-overexpressing pancreatic cancer cells in the dismantling of perineural barriers during neural invasion.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"60 ","pages":"Article 101126"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025417","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":"Optimal radiation dose to induce an abscopal effect by combining carbon-ion radiotherapy and anti-CTLA4 antibody","authors":"Liqiu Ma ,&nbsp;Yang Li ,&nbsp;Yoshimitsu Sakamoto ,&nbsp;Lin Xie ,&nbsp;Saaya Suzuki ,&nbsp;Yukari Yoshida ,&nbsp;Li Sui ,&nbsp;Gang Guo ,&nbsp;Jialing Wen ,&nbsp;Wangcai Ren ,&nbsp;Kazuhiro Kakimi ,&nbsp;Kensuke Osada ,&nbsp;Akihisa Takahashi ,&nbsp;Takashi Shimokawa","doi":"10.1016/j.neo.2024.101099","DOIUrl":"10.1016/j.neo.2024.101099","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Although carbon-ion radiotherapy (CIRT) has led to good outcomes, controlling metastasis is still crucial for improving overall survival. This study aimed to evaluate the effectiveness of by two combinations, one of CIRT and anti-CTLA4 antibody, the other of CIRT and anti-PD-1 antibody, applied at different radiation doses for distal tumour and metastasis suppression.</div></div><div><h3>Materials and methods</h3><div>Murine cancer cells (colon carcinoma Colon-26 cells for experiments and osteosarcoma LM8 cells for verification) were grafted into both sides of the hind legs of syngeneic mice. Right-side tumours were irradiated with 3 Gy or 10 Gy CIRT while the left-side tumours were not irradiated, followed by the administration of the anti-CTLA4 antibody or anti-PD-1 antibody. The diameter of the tumours in both legs was measured 3 times per week after irradiation. The number of pulmonary metastases was evaluated within 3 weeks after irradiation.</div></div><div><h3>Results</h3><div>Compared with the control group, the high-dose group showed promising anti-cancer benefits in terms of both irradiated tumours and lung metastasis, but neither 10 Gy CIRT combined with the anti-CTLA4 antibody nor 10 Gy CIRT combined with the anti-PD-1 antibody suppressed the growth of distant unirradiated tumours. In the low-dose group, the effect on primary tumour control was slightly weaker than that in the high-dose treatment group, but significant suppressive effects on both distant unirradiated tumours and metastases were observed following 3 Gy CIRT combined with anti-CTLA4 antibody treatment. Specifically, the volume of distant unirradiated tumours decreased by 40 % compared with that of the control group, and no lung metastasis was observed.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that there is an optimal dose range for the abscopal effect generated with the CIRT combined with anti-CTLA4 antibody, and it highlights a new opportunity for increased induction efficiency of the abscopal effect of combination therapy.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"60 ","pages":"Article 101099"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824121","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":"Clinical and genetic drivers of oligo-metastatic disease in colon cancer","authors":"Alessandro Ottaiano ,&nbsp;Mariachiara Santorsola ,&nbsp;Roberto Sirica ,&nbsp;Annabella Di Mauro ,&nbsp;Antonella Di Carlo ,&nbsp;Monica Ianniello ,&nbsp;Francesco Sabbatino ,&nbsp;Rosa Castiello ,&nbsp;Francesca Del Peschio ,&nbsp;Marco Cascella ,&nbsp;Francesco Perri ,&nbsp;Maurizio Capuozzo ,&nbsp;Nicola Martucci ,&nbsp;Edoardo Mercadante ,&nbsp;Valentina Borzillo ,&nbsp;Rossella Di Franco ,&nbsp;Francesco Izzo ,&nbsp;Vincenza Granata ,&nbsp;Carmine Picone ,&nbsp;Antonella Petrillo ,&nbsp;Giovanni Savarese","doi":"10.1016/j.neo.2024.101111","DOIUrl":"10.1016/j.neo.2024.101111","url":null,"abstract":"<div><h3>Background</h3><div>Oligo-metastatic disease (OMD) in colon cancer patients exhibits distinct clinical behavior compared to poly-metastatic disease (PMD), with a more responsive and indolent course. This study aims to identify clinical and biological factors uniquely associated with oligo-metastatic behavior.</div></div><div><h3>Methods</h3><div>Metastatic colon cancer patients from an academic center underwent genetic characterization. OMD was defined as ≤3 lesions per organ, each with a total diameter &lt;70 mm and none exceeding 25 mm. Tumor DNA sequencing by NGS utilized the TruSight Oncology 500 kit. Overall survival (OS) was determined from metastasis diagnosis until death using Kaplan–Meier analysis. Multivariate Cox regression examined prognostic links between clinicopathological and genetic factors. Associations with metastatic patterns were evaluated using Chi-square.</div></div><div><h3>Results</h3><div>The analysis involved 104 patients (44 with OMD, 60 with PMD). OMD was more prevalent in males (<em>P</em> = 0.0299) and with single organ involvement (<em>P</em> = 0.0226). Multivariate analysis adjusted for age (&gt;70 vs. &lt;70 years), gender (male vs. female), tumor side (right vs. left), metastatic involvement (more than one site vs. one site), response to first-line therapy (disease control vs. no disease control), and <em>RAS</em>/<em>BRAF</em> variants (wild-type vs. mutated) identified OMD vs. PMD as the strongest independent predictor of survival (HR: 0.14; 95 % CI: 0.06-0.33; <em>P</em>&lt;0.0001). OMD patients exhibited distinct molecular characteristics, including lower frequencies of <em>BRAF</em> p.V600E (P=0.0315) and <em>KRAS</em> mutations (P=0.0456), as well as a higher frequency of high tumor mutational burden (<em>P</em>=0.0127). Additionally, by integrating data from public datasets and our case study, we hypothesize that some gene alterations (i.e.: <em>BRAF, SMAD4, RAF1</em>, and <em>mTOR</em>) may prevent OMD occurrence.</div></div><div><h3>Conclusion</h3><div>OMD, characterized by male predominance, single-site involvement, and distinct molecular features in colon cancer, suggests the need for tailored management strategies.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"60 ","pages":"Article 101111"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878349","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":"Incidence, mortality, and global burden of retinoblastoma in 204 countries worldwide from 1990 to 2021: Data and systematic analysis from the Global Burden of Disease Study 2021","authors":"Linyan Wang ,&nbsp;Jianing Chen ,&nbsp;Yunhan Shen ,&nbsp;Grace Loy Ming Hooi ,&nbsp;Shuohan Wu ,&nbsp;Feng Xu ,&nbsp;Hao Pei ,&nbsp;Jianpeng Sheng ,&nbsp;Tiansheng Zhu ,&nbsp;Juan Ye","doi":"10.1016/j.neo.2024.101107","DOIUrl":"10.1016/j.neo.2024.101107","url":null,"abstract":"<div><h3>Background</h3><div>Retinoblastoma (Rb), the primary intraocular malignancy in children, poses significant risks, yet its overall burden remains inadequately assessed. This study aims to analyze global Rb trends using Global Burden of Disease, Injuries, and Risk Factors study (GBD) 2021 data.</div></div><div><h3>Methods</h3><div>GBD 2021 data was analyzed to assess Rb incidence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021. Average annual percentage changes (AAPCs) were calculated across genders, age groups (0-9 years), and geographic regions categorized by socio-demographic index (SDI) quintiles.</div></div><div><h3>Results</h3><div>From 1990 to 2021, the global Rb age-standardized incidence rate (ASIR) increased from 0.08 (per 100,000, range: 0.05 to 0.10) to 0.09 (per 100,000, range: 0.06 to 0.13). ASIR was not significantly correlated with SDI (R = -0.095, P = 0.18), while age-standardized DALYs rate (R = -0.693, P &lt; 0.001) and age-standardized mortality rate (ASMR) (R = -0.71, P &lt; 0.001) were significantly and negatively correlated with SDI. Increases in ASIR were concentrated in Asia, Europe, and northern and southern Africa. The highest standardized DALYs and ASMR were noted in certain countries in Asia, Europe, and South Africa. Among age groups, the highest disease burdens were observed in the “0-6 days” and “2-4 years” groups. There were no significant gender differences in Rb burden globally.</div></div><div><h3>Conclusions</h3><div>Despite global progress, regions with lower SDI face elevated Rb burden and mortality. Females exhibit higher burdens during infancy, necessitating further investigation. Effective Rb management in resource-limited areas requires international collaboration focused on health education, early diagnosis, and prenatal screening for high-risk families.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"60 ","pages":"Article 101107"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899613","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":"True cancer stem cells exhibit relative degrees of dormancy and genomic stability","authors":"Sanford H. Barsky ,&nbsp;Krista Mcphail ,&nbsp;Justin Wang ,&nbsp;Jordan Dillard ,&nbsp;Crystal J. Beard ,&nbsp;Yin Ye","doi":"10.1016/j.neo.2025.101127","DOIUrl":"10.1016/j.neo.2025.101127","url":null,"abstract":"<div><h3>Background</h3><div>Cancer stem cells in human tumors have been defined by stem cell markers, embryonal signaling pathways and characteristic biology, ie., namely the ability to repopulate the proliferating population. However, even if these properties can be demonstrated within a tumor cell subpopulation, it does not mean that they are truly hierarchical stem cells because they could have been derived from the proliferating population in a reversible manner.</div></div><div><h3>Methods</h3><div>Using a human PDX, Mary-X, that overall expressed a strong cancer stem cell phenotype, the study conducted both GPP-labelled retroviral transfection and fluorescent microsphere uptake studies to distinguish proliferating from dormant cells and array CGH to identify regions of amplifications (gains) and deletions (losses) on the overall Mary-X population and then applied derived probes by FISH on individual cells to identify a genomically stable subpopulation.</div></div><div><h3>Results</h3><div>Whereas 97-99 % of the cells expressed retroviral GFP and not fluorescent particles and showed numerous gene amplifications and deletions, approximately 1-3 % of the cells showed the opposite. The subpopulation with the retained fluorescent microspheres and exhibiting genomic stability was significantly smaller in size than their GFP-expressing and genomically unstable counterparts. Sorting Mary-X spheroids on the basis of either CD133 or ALDH positivity further enriched for this subpopulation.</div></div><div><h3>Conclusions</h3><div>These studies indicate that a truly biological cancer stem cell subpopulation exists that exhibits both dormancy and genomic stability. This subpopulation could not have been derived from the proliferating and resulting genomically unstable population and therefore represents a truly hierarchical stem cell subpopulation capable of only unidirectional differentiation.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"60 ","pages":"Article 101127"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030095","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":"Corrigendum to “p85α Inactivates MMP-2 and Suppresses Bladder Cancer Invasion by Inhibiting MMP-14 Transcription and TIMP-2 Degradation” [Neoplasia (2019) 21, 908–920]","authors":"Jingjing Wang ,&nbsp;Ning Zhang ,&nbsp;Minggang Peng ,&nbsp;Xiaohui Hua ,&nbsp;Chao Huang ,&nbsp;Zhongxian Tian ,&nbsp;Qipeng Xie ,&nbsp;Junlan Zhu ,&nbsp;Jingxia Li ,&nbsp;Haishan Huang ,&nbsp;Chuanshu Huang","doi":"10.1016/j.neo.2024.101095","DOIUrl":"10.1016/j.neo.2024.101095","url":null,"abstract":"","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"60 ","pages":"Article 101095"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899590","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 brain dissemination of glioblastoma requires transdifferentiation into endothelial-like cells via TGF-β-ALK1-Smad1/5 signaling","authors":"Thomas M.B. Ware ,&nbsp;Adilson Fonseca Teixeira ,&nbsp;Josephine Iaria ,&nbsp;Rodney B. Luwor ,&nbsp;Hong-Jian Zhu","doi":"10.1016/j.neo.2024.101110","DOIUrl":"10.1016/j.neo.2024.101110","url":null,"abstract":"<div><div>Glioblastoma is the most aggressive type of brain cancer, but treatment improvements for glioblastoma patients remain stagnated for over 20 years. This is despite the large number of clinical trials that have attempted to replicate the success of therapeutics developed for other cancer types. This discrepancy highlights the urgent need to decipher the unique biology of glioblastomas. Here, we show that glioblastoma tumour cells are highly plastic, integrating into blood vessel walls to disseminate throughout the brain. This relies on the transdifferentiation of glioblastoma tumor cells into endothelial-like cells in a process we termed endothelialisation. Mechanistically, in addition to TGF-β-ALK5-Smad2/3 signaling, glioblastoma tumour cells also activate TGF-β-ALK1-Smad1/5 signaling – a mechanism previously thought to be limited to endothelial cells. Consequently, therapeutic targeting of TGF-β-ALK1-Smad1/5 activity impaired endothelialisation-driven glioblastoma progression. This study identifies a previously unknown component of glioblastoma biology and establishes a therapeutic approach to reduce the progression of this disease.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"60 ","pages":"Article 101110"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899694","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":"Acquired vulnerability against EGF receptor inhibition in gastric cancer promoted by class I histone deacetylase inhibitor entinostat","authors":"Tamara Zenz ,&nbsp;Robert Jenke ,&nbsp;Denys Oliinyk ,&nbsp;Sandra Noske ,&nbsp;René Thieme ,&nbsp;Tim Kahl ,&nbsp;Ines Gockel ,&nbsp;Florian Meier-Rosar ,&nbsp;Achim Aigner ,&nbsp;Thomas RH Büch","doi":"10.1016/j.neo.2024.101121","DOIUrl":"10.1016/j.neo.2024.101121","url":null,"abstract":"<div><h3>Introduction</h3><div>Histone deacetylase inhibitors (HDACi) have shown promising preclinical activity in gastric cancer cells; unfortunately, however, these could not be confirmed in clinical trials. This highlights the need for the identification of underlying reasons, which may also provide the basis for possible combination therapies. Here, we delineated the effects of HDACi on components of EGFR signalling in gastric cancer cells.</div></div><div><h3>Methods</h3><div>We investigated entinostat effects on EGFR and amphiregulin (AREG) expression in various cell line- and primary patient tumor-based <em>in vitro, ex vivo</em> and <em>in vivo</em> models, on the mRNA and protein level. Based on these results, a combined entinostat plus EGFR inhibitor erlotinib treatment <em>in vitro</em> and <em>in vivo</em> was studied.</div></div><div><h3>Results</h3><div>Proteomics analyses in gastric cancer cells treated with entinostat revealed a marked upregulation of EGFR in the majority of cell lines and an even more robust induction of the EGFR ligand AREG. This was confirmed in a panel of different cell lines <em>in vitro</em>, in tumor tissue-slice cultures <em>ex vivo</em> and in cell line- or patient-derived tumor xenografts in mice. Since previous studies in other tumor entities showed a downregulation of EGFR by HDACi, our findings thus indicate essential differences in the adaptive response of gastric carcinoma cells. Moreover, our results provided the basis for combined entinostat + EGFR inhibitor (erlotinib) treatment, and indeed we demonstrate synergistic effects in combination therapy studies.</div></div><div><h3>Conclusion</h3><div>Our findings establish the profound upregulation of the EGFR/AREG axis by entinostat as starting point for a rational combination therapy in gastric carcinoma.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"60 ","pages":"Article 101121"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048349","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":"Transcriptomic and proteomic profiling identifies feline fibrosarcoma as clinically amenable model for aggressive sarcoma subtypes","authors":"Mikiyo Weber ,&nbsp;Daniel Fuchs ,&nbsp;Amiskwia Pöschel ,&nbsp;Erin Beebe ,&nbsp;Zuzana Garajova ,&nbsp;Armin Jarosch ,&nbsp;Laura Kunz ,&nbsp;Witold Wolski ,&nbsp;Lennart Opitz ,&nbsp;Franco Guscetti ,&nbsp;Mirja C. Nolff ,&nbsp;Enni Markkanen","doi":"10.1016/j.neo.2024.101104","DOIUrl":"10.1016/j.neo.2024.101104","url":null,"abstract":"<div><div>Fibrosarcomas (FSA) are malignant mesenchymal tumors characterized by low chemo- and radiosensitivity. Development of novel treatment strategies for human adult FSA is hindered by the low incidence and the absence of suitable clinical models. Interestingly, aggressive FSA occur more frequently in domestic cats, hence potentially representing a clinically amenable model to assess novel therapies such as targeted imaging or theranostics. However, a lack of molecular characterization of FSA and adjacent normal tissue (NT) in both species hinders identification of tumor-specific targets and undermines the translational potential of feline FSA. Combining laser-capture microdissection, RNAsequencing and liquid chromatography-tandem mass spectrometry, we perform comprehensive profiling of 30 feline FSA and matched skeletal muscle, adipose and connective tissue. Clear inter-tissue differences allow identification of significantly upregulated and tumor-exclusive features that represent potential targets for diagnostic and therapeutic approaches. While feline FSA are characterized by hyperactive EIF2, TP53 and MYC signaling, immune-related and neuronal pathways emerge as modulators of tumor aggressiveness and immunosuppression. A high degree of molecular similarity with canine and adult FSA allows identification of tumor targets that are conserved across species. Significant enrichment in DNA repair pathways in feline FSA correlate with aggressive clinical behavior in human soft-tissue sarcoma. Finally, we leverage the molecular profiles to identify vulnerabilities, including sensitivity to ATR and PARP inhibition as potential treatment for feline FSA. In conclusion, this detailed landscape provides a rich resource to identify target candidates and therapeutic vulnerabilities within and across species and supports feline FSA as relevant models for the human disease.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"60 ","pages":"Article 101104"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11713505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839946","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":"Informatics strategies for early detection and risk mitigation in pancreatic cancer patients","authors":"Di Jin ,&nbsp;Najeeb Ullah Khan ,&nbsp;Wei Gu ,&nbsp;Huijun Lei ,&nbsp;Ajay Goel ,&nbsp;Tianhui Chen","doi":"10.1016/j.neo.2025.101129","DOIUrl":"10.1016/j.neo.2025.101129","url":null,"abstract":"<div><div>This review provides a comprehensive overview of the current landscape in pancreatic cancer (PC) screening, diagnosis, and early detection. This emphasizes the need for targeted screening in high-risk groups, particularly those with familial predispositions and genetic mutations, such as BRCA1, BRCA2, and PALB2. This review highlights the sporadic nature of most PC cases and significant risk factors, including smoking, alcohol consumption, obesity, and diabetes. Advanced imaging techniques, such as Endoscopic Ultrasound (EUS) and Contrast-Enhanced Harmonic Imaging (CEH-EUS), have been discussed for their superior sensitivity in early detection. This review also explores the potential of novel biomarkers, including those found in body fluids, such as serum, plasma, urine, and bile, as well as the emerging role of liquid biopsy technologies in analyzing circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and exosomes. AI-driven approaches, such as those employed in Project Felix and CancerSEEK, have been highlighted for their potential to enhance early detection through deep learning and biomarker discovery. This review underscores the importance of universal genetic testing and the integration of AI with traditional diagnostic methods to improve outcomes in high-risk individuals. Additionally, this review points to future directions in PC diagnostics, including next-generation imaging, molecular biomarkers, and personalized medicine, aiming to overcome current diagnostic challenges and improve survival rates. Ultimately, the review advocates the adoption of informatics and AI-driven strategies to enhance early detection, reduce morbidity, and save lives in the fight against pancreatic cancer.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"60 ","pages":"Article 101129"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025414","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}