Cancer prevention research (Philadelphia, Pa.)最新文献

{"title":"Editors' Selections from Relevant Scientific Publications.","authors":"","doi":"10.1158/1940-6207.CAPR-17-10-HFL","DOIUrl":"https://doi.org/10.1158/1940-6207.CAPR-17-10-HFL","url":null,"abstract":"","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":"17 10","pages":"441"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preventive Treatment with a CD73 Small Molecule Inhibitor Enhances Immune Surveillance in K-Ras Mutant Pancreatic Intraepithelial Neoplasia.","authors":"Lincoln N Strickland, Wendao Liu, Usama Hussein, Nicolette Mardik, Xian Chen, Tingting Mills, Lana A Vornik, Michelle I Savage, Shizuko Sei, John Clifford, Holger K Eltzschig, Powel H Brown, Zhongming Zhao, Florencia McAllister, Jennifer M Bailey-Lundberg","doi":"10.1158/1940-6207.CAPR-24-0200","DOIUrl":"10.1158/1940-6207.CAPR-24-0200","url":null,"abstract":"<p><p>Immunoprevention is an emerging consideration for solid tumors, including pancreatic ductal adenocarcinoma (PDAC). We and others have shown that Kras mutations in genetic models of spontaneous pancreatic intraepithelial neoplasia (PanIN), which is a precursor to PDAC, results in CD73 expression in the neoplastic epithelium and some populations of infiltrating immune cells, including macrophages and CD8 T cells. CD73 is an ecto-enzyme that converts extracellular adenosine monophosphate to adenosine, a critical immune inhibitory molecule in PDAC. We hypothesized inhibition of CD73 would reduce the incidence of PanIN formation and alter the immune microenvironment. To test our hypothesis, we used the KrasG12D; PdxCre1 (KC) genetically engineered mouse model and tested the utility of AB-680, a small molecule inhibitor targeting CD73, to inhibit PanIN progression. AB-680, or vehicle control, was administered using oral gavage delivery 3 days/week at 10 mg/kg, beginning when the mice were 2 months old and lasting 3 months. We euthanized the mice at 5 months old. In the KC model, we quantified significantly less pancreatitis, early and advanced PanIN, and quantified a significant increase in M1 macrophages in AB-680-treated mice. Single-cell RNA sequencing (scRNA-seq) of pancreata of AB-680-treated mice revealed increased infiltration of CD4+ T cells, CD8+ T cells, and mature B cells. The scRNA-seq analysis showed that CD73 inhibition reduced M2 macrophages, acinar, and PanIN cell populations. CD73 inhibition enhanced immune surveillance and expanded unique clonotypes of TCR and BCR, indicating that inhibition of CD73 augments adaptive immunity early in the neoplastic microenvironment. Prevention Relevance: Previous studies found PanIN lesions in healthy pancreata. Not all progress to PDAC, suggesting a window for enhanced antitumor immunity through immunoprevention therapy. CD73 inhibition in our study prevents PanIN progression, reduces immune-suppressive macrophages and expands TCR and BCR unique clonotypes, highlighting an encouraging therapeutic avenue for high-risk individuals.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"457-470"},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing Colorectal Cancer Screening with Droplet Digital PCR Analysis of Fusobacterium nucleatum in Fecal Immunochemical Test Samples.","authors":"José G Datorre, Mariana B Dos Reis, Ana C de Carvalho, Jun Porto, Gabriela H Rodrigues, Adhara B Lima, Monise T Reis, Welinton Hirai, Claudio L Hashimoto, Denise P Guimarães, Rui M Reis","doi":"10.1158/1940-6207.CAPR-23-0331","DOIUrl":"10.1158/1940-6207.CAPR-23-0331","url":null,"abstract":"<p><p>Fecal immunochemical test (FIT) followed by colonoscopy in positive cases is commonly used for population-based colorectal cancer screening. However, specificity of FIT for colorectal cancer is not ideal and has poor performance for advanced adenoma detection. Fecal Fusobacterium nucleatum (Fn) detection has been proposed as a potential noninvasive biomarker for colorectal cancer and advanced adenoma detection. We aimed to evaluate the diagnostic performance of Fn detection using droplet digital PCR (ddPCR) in FIT samples from individuals enrolled in a colorectal cancer screening program with colorectal adenoma or cancer. We evaluated Fn presence in DNA isolated from FIT leftover material of 300 participants in a colorectal cancer screening program using ddPCR. The Fn DNA amount was classified as Fn-low/negative and Fn-high, and the association with patients' clinicopathological features and accuracy measurements was calculated. Fn-high levels were more prevalent in FIT-positive (47.2%, n = 34 of 72) than FIT-negative samples (28.9%, n = 66 of 228; P < 0.04). Among FIT-positive samples, high Fn levels were significantly more frequent in patients with cancer (CA, n = 8) when compared to normal (NT, n = 16; P = 0.02), non-advanced adenomas (NAA, n = 36; P = 0.01), and advanced adenomas (AA, n = 12; P = 0.01). Performance analysis of Fn in FIT-positive samples for colorectal cancer detection yielded an AUC of 0.8203 [confidence interval (CI), 0.6464-0.9942], with high sensitivity (100%) and specificity of 50%. Concluding, we showed the feasibility of detecting Fn in FIT leftovers using the ultrasensitive ddPCR technique. Furthermore, we highlighted the potential use of Fn levels in fecal samples to ameliorate colorectal cancer detection. Prevention Relevance: Fusobacterium nucleatum detection by droplet digital PCR could prioritize the selection of fecal immunochemical test-positive individuals who might benefit the most from the colonoscopy procedure.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"471-479"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141478091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarker-Driven Personalized Immunoprevention: Toward More Efficient Clinical Trials?","authors":"Sai Yendamuri, Konstantin H Dragnev","doi":"10.1158/1940-6207.CAPR-24-0234","DOIUrl":"10.1158/1940-6207.CAPR-24-0234","url":null,"abstract":"<p><p>In this secondary analysis of specimens from the CANTOS trial, the investigators find that patients with clonal hematopoiesis mutations, particularly in the TET2 gene, predict a benefit of decreased cancer risk with the administration of the anti-IL1β agent canakinumab. Despite small numbers and the need for prospective validation, the findings are exciting as they demonstrate the potential for personalized chemoprevention approaches. Such personalized approaches can potentially enhance the feasibility of cancer prevention trials. See related article by Woo et al., p. 429.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"399-400"},"PeriodicalIF":0.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141332629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lung Microbiome in Lung Cancer: A New Horizon in Cancer Study.","authors":"Pragya Kashyap, Naveen Dutt, Dinesh K Ahirwar, Pankaj Yadav","doi":"10.1158/1940-6207.CAPR-24-0147","DOIUrl":"10.1158/1940-6207.CAPR-24-0147","url":null,"abstract":"<p><p>Lung cancer is the second most prevalent cancer worldwide and a leading cause of cancer-related deaths. Recent technological advancements have revealed that the lung microbiome, previously thought to be sterile, is host to various microorganisms. The association between the lung microbiome and lung cancer initiation, progression, and metastasis is complex and contradictory. However, disruption in the homeostasis of microbiome compositions correlated with the increased risk of lung cancer. This review summarizes current knowledge about the most recent developments and trends in lung cancer-related microbiota or microbial components. This article aims to provide information on this rapidly evolving field while giving context to the general role of the lung microbiome in lung cancer. In addition, this review briefly discussed the causative association of lung microbiome with lung cancer. We will review the mechanisms by which lung microbiota influence carcinogenesis, focusing on microbiota dysbiosis. Moreover, we will also discuss the host-microbiome interaction as it plays a crucial role in stimulating and regulating the immune response. Finally, we will provide information on the diagnostic role of the microbiome in lung cancer. This article aims to offer an overview of the lung microbiome as a predictive and diagnostic biomarker in lung cancer.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"401-414"},"PeriodicalIF":0.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editors' Selections from Relevant Scientific Publications.","authors":"","doi":"10.1158/1940-6207.CAPR-17-9-HFL","DOIUrl":"https://doi.org/10.1158/1940-6207.CAPR-17-9-HFL","url":null,"abstract":"","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":"17 9","pages":"397"},"PeriodicalIF":0.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editors' Selections from Relevant Scientific Publications.","authors":"","doi":"10.1158/1940-6207.CAPR-17-8-HFL","DOIUrl":"https://doi.org/10.1158/1940-6207.CAPR-17-8-HFL","url":null,"abstract":"","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":"17 8","pages":"347"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Colon Age: A Metric for Whether and How to Screen Male Veterans for Early-Onset Colorectal Cancer.","authors":"Thomas F Imperiale, Laura J Myers, Barry C Barker, Timothy E Stump, Joanne K Daggy","doi":"10.1158/1940-6207.CAPR-23-0544","DOIUrl":"10.1158/1940-6207.CAPR-23-0544","url":null,"abstract":"<p><p>We aimed to develop a metric for estimating risk for early-onset colorectal cancer (EOCRC) to help decide whether and how to screen persons < age 50. We used risk prediction models derived and validated on male Veterans to calculate the relative risks (RRs) for 6 scenarios: one low-risk scenario (no risk factors present), four intermediate risk scenarios (some factors present), and one high-risk scenario (all factors present) for three age groups (35-39, 40-44, and 45-49 years). For each scenario, we estimated absolute CRC risk using SEER CRC incidence rates and each scenario's RR. We identified the current SEER 5-year age group to which the revised estimate was closest and refer to the midpoint of this group as the \"colon age\". When the revised estimate was ≥ that for 50-54-year-olds and for 70-74-year-olds, respective recommendations were made for (any) CRC screening and screening with colonoscopy. Among the scenarios, there was inconsistency between the two models for the 35-39 and 40-44 age groups, with only the 15-variable model recommending screening for the higher-risk 35-to-39-year-olds. Both models recommended screening for some intermediate risk and high-risk 40-44-year-olds. The models were well-aligned on whether and how to screen most 45-49-year-olds. Using risk factors for EOCRC with CRC incidence rates, \"colon age\" may be useful for shared decision making about whether and how to screen male Veterans < 50 years. For 45-49-year-olds, the 7-variable model may be preferred by patients, providers, and health systems.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"377-84"},"PeriodicalIF":2.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiyear Clinical Outcomes of Cancers Diagnosed Following Detection by a Blood-Based Multicancer Early Detection Test.","authors":"Adam H Buchanan, Anne M Lennon, Omair A Choudhry, Paul Z Elias, Seema P Rego, Jennifer R Sadler, Julia Roberta, Yongqiang Zhang, Darl D Flake, Zachary M Salvati, Eric S Wagner, Elliot K Fishman, Nickolas Papadopoulos, Tomasz M Beer","doi":"10.1158/1940-6207.CAPR-24-0107","DOIUrl":"10.1158/1940-6207.CAPR-24-0107","url":null,"abstract":"<p><p>In the US, <20% of cancers are diagnosed by standard-of-care (SoC) screening. Multicancer early detection (MCED) tests offer the opportunity to expand cancer screening. Understanding the characteristics and clinical outcomes of MCED-detected cancers is critical to clarifying MCED tests' potential impact. DETECT-A is the first prospective interventional trial of an MCED blood test (CancerSEEK). CancerSEEK, coupled with diagnostic PET-CT, identified cancers including those not detected by SoC screening, the majority of which were localized or regional. We report multiyear outcomes in patients with cancers diagnosed following a positive CancerSEEK test. Nine cancer types were diagnosed in 26 participants whose cancers were first detected by CancerSEEK. Information on cancer diagnoses, treatments, and clinical outcomes was extracted from medical records through November 2022. Data collection occurred at a median of 4.4 years (IQR: 4.1-4.6) following study enrollment. Thirteen of 26 (50%) participants were alive and cancer-free [ovarian (4), thyroid (1), uterine (2), breast (1), colorectal (2), and lung (3)]; 7/13 (54%) had cancers without recommended SoC screening modalities. All eight treated stage I or II participants (8/8, 100%) and 12/14 (86%) surgically treated participants were alive and cancer-free. Eligibility for surgical treatment was associated with favorable multiyear outcomes (P = 0.0002). Half of participants with MCED-detected cancers were alive and cancer-free after 4.4 years median follow-up. Most were diagnosed with early-stage cancers and were treated surgically. These results suggest that early cancer detection by CancerSEEK may have facilitated curative-intent treatments and associated positive clinical outcomes in some DETECT-A participants. Prevention Relevance: This study provides preliminary evidence of the potential of multicancer early detection testing as an effective screening tool for detecting cancers without standard-of-care (SoC) screening modalities and complementing SoC cancer screening.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"349-353"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11292316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141181675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Past and Future of Angiogenesis as a Target for Cancer Therapy and Prevention.","authors":"Adriana Albini, Douglas M Noonan, Paola Corradino, Francesca Magnoni, Giovanni Corso","doi":"10.1158/1940-6207.CAPR-24-0085","DOIUrl":"10.1158/1940-6207.CAPR-24-0085","url":null,"abstract":"<p><p>Cancer growth is dependent on angiogenesis, the formation of new blood vessels, which represents a hallmark of cancer. After this concept was established in the 1970s, inhibition of tumor development and metastases by blocking the neoangiogenic process has been an important approach to the treatment of tumors. However, antiangiogenic therapies are often administered when cancer has already progressed. The key to reducing the cancer burden is prevention. We noticed 20 years ago that a series of possible cancer chemopreventive agents showed antiangiogenic properties when tested in experimental models. This article reviews the relevant advances in the understanding of the rationale for targeting angiogenesis for cancer therapy, prevention, and interception and recently investigated substances with antiangiogenic activity that may be suitable for such strategies. Many compounds, either dietary derivatives or repurposed drugs, with antiangiogenic activity are possible tools for cancer angioprevention. Such molecules have a favorable safety profile and are likely to allow the prolonged duration necessary for an efficient preventive strategy. Recent evidence on mechanisms and possible use is described here for food derivatives, including flavonoids, retinoids, triterpenoids, omega fatty acids, and carotenoids from marine microorganisms. As examples, a number of compounds, including epigallocatechin, resveratrol, xanthohumol, hydroxytyrosol, curcumin, fenretinide, lycopene, fucoxanthin, and repurposed drugs, such as aspirin, β blockers, renin-angiotensin-aldosterone inhibitors, carnitines, and biguanides, are reviewed.</p>","PeriodicalId":72514,"journal":{"name":"Cancer prevention research (Philadelphia, Pa.)","volume":" ","pages":"289-303"},"PeriodicalIF":0.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}