Oncoscience最新文献

{"title":"Correction: Lactate dehydrogenase A inhibition by small molecular entities: steps in the right direction.","authors":"Btissame El Hassouni,&nbsp;Marika Franczak,&nbsp;Mjriam Capula,&nbsp;Christian M Vonk,&nbsp;Valentina M Gomez,&nbsp;Ryszard T Smolenski,&nbsp;Carlotta Granchi,&nbsp;Godefridus J Peters,&nbsp;Filippo Minutolo,&nbsp;Elisa Giovannetti","doi":"10.18632/oncoscience.529","DOIUrl":"https://doi.org/10.18632/oncoscience.529","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.18632/oncoscience.519.].</p>","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38897114","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 helix-loop-helix transcriptional regulator Id4 is required for terminal differentiation of luminal epithelial cells in the prostate.","authors":"Dhanushka Hewa Bostanthirige, Shravan K Komaragiri, Jugal B Joshi, Majid Alzahrani, Isha Saini, Sanjay Jain, Nathan J Bowen, Matthew C Havrda, Jaideep Chaudhary","doi":"10.18632/oncoscience.524","DOIUrl":"10.18632/oncoscience.524","url":null,"abstract":"<p><p>Inhibitor of differentiation 4 (Id4), a member of the helix-loop-helix family of transcriptional regulators has emerged as a tumor suppressor in prostate cancer. In this study we investigated the effect of loss of Id4 (<i>Id4-/-</i>) on mouse prostate development. Histological analysis was performed on prostates from 25 days, 3 months and 6 months old <i>Id4-/-</i> mice. Expression of Amacr, Ck8, Ck18, Fkbp51, Fkbp52, androgen receptor, Pten, sca-1 and Nkx3.1 was investigated by immunohistochemistry. Results were compared to the prostates from <i>Nkx3.1-/-</i> mice. <i>Id4-/-</i> mice had smaller prostates with fewer and smaller tubules. Subtle PIN like lesions were observed at 6mo. Decreased Nkx3.1 and Pten and increased stem cell marker sca-1, PIN marker Amacr and basal cell marker p63 was observed at all ages. Persistent Ck8 and Ck18 expression suggested that loss of Id4 results in epithelial commitment but not terminal differentiation in spite of active Ar. Loss of Id4 attenuates normal prostate development and promotes hyperplasia/ dysplasia with PIN like lesions. The results suggest that loss of Id4 maintains stem cell phenotype of \"luminal committed basal cells\", identifying a unique prostate developmental pathway regulated by Id4.</p>","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38897109","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":"Balancing efficacy and quality of life measurements among metastatic renal cell carcinoma (RCC) studies.","authors":"Jeanny B Aragon-Ching","doi":"10.18632/oncoscience.528","DOIUrl":"https://doi.org/10.18632/oncoscience.528","url":null,"abstract":"<p><p>Metastatic renal cell carcinoma (mRCC) treatments have rapidly evolved in the last few years. While vascular endothelial growth factor (VEGF) inhibition had previously been the mainstay of treatment for first-line advanced RCC therapy in the past decade, it has now rapidly changed into combination checkpoint inhibitors with or without VEGF TKIs, although there remains a role for VEGF tyrosine kinase inhibitor monotherapy for patients with favorable-risk disease and for those with intermediate and poor-risk disease with the use of cabozantinib. Perspectives on the Quality-adjusted survival Time without Symptoms of disease or Toxicity (Q-TWiST) analysis for the CABOSUN trial, as well as different aspects of efficacy regarding different first-line therapy for advanced or metastatic RCC are discussed herein.</p>","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38897113","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":"Upper gastrointestinal cancers in Lynch syndrome: the time for surveillance is now.","authors":"Shria Kumar,&nbsp;Bryson W Katona","doi":"10.18632/oncoscience.525","DOIUrl":"https://doi.org/10.18632/oncoscience.525","url":null,"abstract":"","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38897110","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":"Causation of increased prostate cancer in young men.","authors":"Archie Bleyer, Filippo Spreafico, Ronald Barr","doi":"10.18632/oncoscience.527","DOIUrl":"10.18632/oncoscience.527","url":null,"abstract":"","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38897112","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":"AKT as a therapeutic target for autophagy induction and cancer therapy.","authors":"Qi Wu,&nbsp;Guido Kroemer,&nbsp;Oliver Kepp","doi":"10.18632/oncoscience.526","DOIUrl":"https://doi.org/10.18632/oncoscience.526","url":null,"abstract":"Qi Wu1,2,3, Yi Tu1, Guido Kroemer2,3,4,5 and Oliver Kepp2,3 1 Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, China 2 Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, France 3 Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Center, Université Paris Saclay, Villejuif, France 4 Suzhou Institute for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, China 5 Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France 6 Karolinska Institutet, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38897111","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":"Monitoring vascular normalization: new opportunities for mitochondrial inhibitors in breast cancer.","authors":"Silvana Mouron,&nbsp;Maria J Bueno,&nbsp;Manuel Muñoz,&nbsp;Miguel Quintela-Fandino","doi":"10.18632/oncoscience.523","DOIUrl":"https://doi.org/10.18632/oncoscience.523","url":null,"abstract":"<p><p>Preclinical evidence indicates the potential of targeting mitochondrial respiration as a therapeutic strategy. We previously demonstrated that mitochondrial inhibitors' efficacy was restricted to a metabolic context in which mitochondrial respiration was the predominant energy source, a situation achievable by inducing vascular normalization/hypoxia correction with antiangiogenics. Using molecular imaging, we showed how the same antiangiogenic agent may display different normalizing properties in patients with the same tumor type. This is of key importance, since patients experiencing normalization seem to get more benefit from standard chemotherapy combinations, and also could be eligible for combination with antimitochondrial agents. This scenario emphasizes the need for monitoring vascular normalization in order to optimize the use of antiangiogenics. We have also proposed a method to evaluate anti-mitochondrial agents' pharmacodynamics; despite promising accuracy in animal studies the clinical results were inconclusive, highlighting the need for research in this field. Regarding patients that respond to antiangiogenics increasing vessel abnormality, in this case an immunosuppressive tumor microenvironment is generated. Whether anti-mitochondrial agents can positively modulate the activity of T effector cell subpopulations remains an area of active research. Our research sheds light on the importance of refining the use of antiangiogenics, highlighting the relevance of tracing vascular normalization as a potential biomarker for antiangiogenics to assist patient-tailored medicine and exploring the role of mitochondrial inhibitors in the context of vascular normalization and correction of hypoxia.</p>","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38885688","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":"Uncovering the deubiquitinase activity landscape of breast cancer.","authors":"Sijia Liu,&nbsp;Peter Ten Dijke","doi":"10.18632/oncoscience.518","DOIUrl":"https://doi.org/10.18632/oncoscience.518","url":null,"abstract":"<p><p>Breast cancer is a highly heterogeneous disease with dynamic changes in the tumor microenvironment. Precision medicine will in the future provide the possibility to treat each individual cancer patient with the right (combination) therapy specifically tailored to personal needs. However, in order to accomplish this, more accurate biomarkers for precise diagnosis, prognosis, therapy response, and target-specific drugs are required. Although an increasing number of (epi)genetic driving alterations have been reported in breast cancer, the major stumbling block for clinical application of many of them is that they are difficult to therapeutically target. Deubiquitinases (DUBs) are emerging drug targets that play important roles in cancer progression. Hence, we devoted our efforts to uncover the global DUB activity landscape of breast cancer in order to discover potential novel biomarkers or therapeutic targets. We developed a specific DUB activity-based inhibitor and probe and applied it to obtain new insights into breast cancer.</p>","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38829905","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":"Dysregulated PJA1-TGF-β signaling in cancer stem cell-associated liver cancers.","authors":"Jian Chen,&nbsp;Julian A Gingold","doi":"10.18632/oncoscience.522","DOIUrl":"https://doi.org/10.18632/oncoscience.522","url":null,"abstract":"<p><p>The transforming growth factor beta (TGF-β) signaling pathway plays important roles in cell differentiation, stem cell modulation, organ lineage, and immune suppression. TGF-β signaling is negatively regulated by the ubiquitin-proteasome pathway. Although mouse models of cancer arising from a defective TGF-β pathway clearly demonstrate the tumor-suppressive role of TGF-β, the underlying mechanism by which a defective TGF-β pathway triggers liver cancer development is poorly understood. This review summarizes key findings from our recent studies connecting TGF-β to hepatic oncogenesis and highlights the vulnerability of TGF-β signaling to PJA1-mediated ubiquitination. TGF-β, together with the chromatin insulator CCCTC-binding factor (CTCF), epigenetically and transcriptionally regulate tumor promoter genes, including IGF2 and TERT, in TGF-β-defective mice and in human liver cancers. Dysfunction of the TGF-β-regulated SPTBN1/SMAD3/CTCF complex increases stem cell-like properties in hepatocellular carcinoma (HCC) cells and enhances tumorigenesis in tumor-initiating cells in a mouse model. PJA1, a novel E3 ubiquitin ligase, is a key negative regulator of TGF-β signaling. PJA1 overexpression is detected in HCCs and is sufficient to suppress SMAD3- and SPTBN1-mediated TGF-β tumor suppressor signaling, promoting HCC proliferation. Dysregulated PJA1-TGF-β signaling activates oncogenic genes and promotes tumorigenesis in human liver cancers. In addition, inhibition of PJA1 by treatment with E3 ligase inhibitors restores TGF-β tumor-suppressor function and suppresses liver cancer progression. These new findings suggest potential therapeutic avenues for targeting dysregulated PJA1-TGF-β signaling via cancer stem cells in liver cancers.</p>","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10343114","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":"Getting quantitative on the effects of somatic mutation on cancer.","authors":"Jeffrey P Townsend","doi":"10.18632/oncoscience.521","DOIUrl":"https://doi.org/10.18632/oncoscience.521","url":null,"abstract":"Numerous powerful bioinformatic analyses of cancer tumor sequencing have applied sophisticated mutation calling, determining the key cancer-causing variants and quantifying their prevalence. The calculations of prevalence of a mutation across tumors and the determination of the statistical significance of whether it is a driver are the “shoulders” that have enabled the build-up to the most useful metrics about cancer variants—metrics which quantify the effect of the variant on replication and survival of the cancer lineage. Ostrow et al [1] effectively and comprehensively applied ratios of non-synonymous change to synonymous change to quantify natural selection in the somatic evolution of cancer, an approach that has been followed by others in different ways and contexts since then [2–4]. Martincorena et al [2] performed a cogent gene-wide analysis using mutation signatures c.f. [5] on the larger data sets available three years later. More recently, it was revealed that previous studies have reported variant prevalence and P value, but have not reported cancer effect sizes, which quantify the effect of natural selection on somatic mutations within cancer cell lineages. Deconvolving the baseline variant mutation rates enables estimation of the selection intensity of individual mutations [6, 7]—a quantification that should be directly interpreted as a cancer lineage effect size that should be used in decision-making. This measure of the effect of specific somatic mutations on cancer cell proliferation and survival should be widely appreciated as a primary consideration of precisionmedicine tumor boards, which are in operation at hospitals around the world. Effect sizes of somatic mutations should also be a key consideration in the initiation and design of precision medicine clinical trials: the number of trials has been increasing so rapidly that some have argued that demand is vastly outpacing the supply of enrollable patients [8]. Effect sizes should guide target selection in pharmacological development, an approximately three billion dollar industry [9]. And gene-specific site-specific effect sizes should guide basic research prioritization toward those important components of molecular and cell biology that have long-term potential to lead to therapies and cures for cancer. There appear to be increasing numbers of drivers in each cancer as we examine larger and larger datasets [10], and each driver has its own quantitative effect on cancer [11]. Decoupling the contributions of mutation and cancer lineage selection to the frequency of somatic variants among tumors is critical to understanding— and predicting—the therapeutic potential of different interventions [12]. Importantly, antagonistic and synergistic epistasis among mutations also impacts the potential therapeutic benefit of targeted drug development [13]. Active use of these quantitative approaches are essential to furthering basic research on cancer, informing clinical practice, and pro","PeriodicalId":19508,"journal":{"name":"Oncoscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38829904","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}