Invited Speaker Abstracts最新文献

{"title":"Abstract ES5-1: Tumor dormancy and recurrence","authors":"L. Chodosh","doi":"10.1158/1538-7445.sabcs18-es5-1","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs18-es5-1","url":null,"abstract":"","PeriodicalId":224797,"journal":{"name":"Invited Speaker Abstracts","volume":"32 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122197742","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":"Abstract TS2-1: The complexity of targeting PI3K for cancer therapy","authors":"L. Cantley","doi":"10.1158/1538-7445.SABCS18-TS2-1","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-TS2-1","url":null,"abstract":"Phosphoinositide 3-Kinase (PI3K) is activated by insulin and other growth factors to mediate cell growth. The PI3K enzyme encoded by the PIK3CA gene is one of the most frequently mutated oncogenes in human cancer. This same enzyme mediates insulin responses in liver, muscle, fat and other tissues. The most common mutations in this gene enhance the ability of PI3K to be activated by insulin. Since breast cancers typically express relatively high levels of the insulin receptor, high serum insulin levels are likely to enhance activation of PI3K in breast cancers. PI3K inhibitors that target PIK3CA have the expected physiological effect of raising serum glucose and insulin levels and the elevated insulin is likely to compromise the effectiveness of therapy. Data will be presented showing that in mouse models of human breast cancers and other cancers, dietary interventions and pharmaceutical interventions that limit elevation of serum insulin during PI3K therapy improve responses to PI3K inhibitors. Citation Format: Cantley L. The complexity of targeting PI3K for cancer therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr TS2-1.","PeriodicalId":224797,"journal":{"name":"Invited Speaker Abstracts","volume":"72 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116010651","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":"Abstract ES4-2: Treatment morbidity and quality of life considerations","authors":"T. Whelan","doi":"10.1158/1538-7445.sabcs18-es4-2","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs18-es4-2","url":null,"abstract":"","PeriodicalId":224797,"journal":{"name":"Invited Speaker Abstracts","volume":"669 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116101929","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":"Abstract ES2-3: Exosome-mediated stimulation of metastasis","authors":"A. Minn","doi":"10.1158/1538-7445.SABCS18-ES2-3","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-ES2-3","url":null,"abstract":"Although cancer cell intrinsic mechanisms are important in driving aggressive features of cancer, stromal cells in the tumor microenvironment also serve critical roles. In particular, heterotypic interaction between cancer cells and stromal fibroblasts can generate signals for cancer progression, therapy resistance, and inflammatory responses. Among the signals resulting from cellular cross-talk include anti-viral pathways that induce interferon-stimulated genes (ISGs). These observations suggest 1) the existence of signals in the tumor microenvironment that mimic a viral infection, 2) resulting activation of anti-viral signaling may contribute to how stromal cells promote aggressive features of cancer, and 3) mechanisms must exist to prevent this anti-viral signaling under non-pathological conditions. We have demonstrated that exosomes and their RNA produced by stromal fibroblasts represents one such “virus mimic” by engaging RNA pattern recognition receptors (PRRs) such as RIG-I. Triggering of stromal NOTCH-MYC by breast cancer cells results in a POL3-driven increase in RN7SL1, an endogenous non-coding RNA normally shielded from PRR recognition by RNA binding proteins SRP9/14. This increase in RN7SL1 alters its stoichiometry with SRP9/14 and generates unshielded RN7SL1 that is deployed in stromal exosomes. After these stromal exosomes are transferred to immune cells, the unshielded RN7SL1 can drive an inflammatory response. Upon exosome transfer to breast cancer cells, unshielded RN7SL1 activates the RIG-I to enhance tumor growth, metastasis, and therapy resistance. The significance of this “virus mimicry” and failure to shield endogenous RN7SL1 from PRR activation is corroborated by evidence from patient tumors and blood. In total, these results demonstrate how exosomes, unshielding of endogenous RNAs, and engagement of pattern recognition receptors couple stromal activation with aggressive features of breast cancer. Citation Format: Minn A. Exosome-mediated stimulation of metastasis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr ES2-3.","PeriodicalId":224797,"journal":{"name":"Invited Speaker Abstracts","volume":"71 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124620024","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":"Abstract CS1-2: Breast cancer genetic testing and results in diverse populations","authors":"A. Kurian","doi":"10.1158/1538-7445.SABCS18-CS1-2","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-CS1-2","url":null,"abstract":"Sequencing multiple (20-100) cancer-associated genes has rapidly become the clinical standard for hereditary cancer risk assessment. In patients with breast cancer and/or ovarian cancer the BRCA1 and BRCA2 genes have been most widely tested, but a significant number of patients are now found to carry pathogenic (or likely pathogenic) variants in many other genes whose cancer risks are less well-characterized. Moreover, multiple-gene sequencing is associated with a higher rate of uncertain results (variants of uncertain significance), which are more prevalent among racial/ethnic minorities. While pathogenic variants in less well-characterized genes are prevalent, the appropriate management of carriers remains unclear. Questions remain about the magnitude of risk associated with a pathogenic variant in a specific gene; the spectrum of associated cancers; and the extent to which these factors are modified by family cancer history. Data are emerging from epidemiologic studies in various settings. However, clinical practice requires real-time decisions about whom to test, and for which cancers to screen, despite an incomplete evidence base. This lecture will review the current state of the science on genetic testing for hereditary breast and ovarian cancer risk. We have recently collaborated with genetic testing laboratories to link the results of clinical genetic testing to Surveillance, Epidemiology and End Results (SEER) registry records of >150,000 breast cancer and/or ovarian cancer patients. I will present results from the SEER-GeneLINK research initiative, focusing on the use, correlates and outcomes of genetic testing on the population level. Citation Format: Kurian A. Breast cancer genetic testing and results in diverse populations [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr CS1-2.","PeriodicalId":224797,"journal":{"name":"Invited Speaker Abstracts","volume":"81 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133441707","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":"Abstract ES6-1: Oxidative stress responses in cancer","authors":"J. Brugge","doi":"10.1158/1538-7445.SABCS18-ES6-1","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-ES6-1","url":null,"abstract":"Generation of reactive oxygen species (ROS), a natural byproduct of oxygen metabolism, occurs in all aerobic organisms at a controlled rate. Cancer cells are subjected to numerous cellular insults, including dysregulated oncogenes and loss of their natural extracellular matrix (ECM) interactions, that lead to the generation of high levels of ROS and selection for upregulation of anti-oxidant programs that allow adaptation to elevated ROS. Although cancer cells possess enhanced canonical antioxidant programs that neutralize ROS, they nevertheless exhibit prominent ROS levels in response to these insults, suggesting the existence of additional programs that allow cancer cells to tolerate elevated ROS. My presentation will include a discussion of the evolving concepts about the role of oxidative stress and anti-oxidants in distinct processes associated with tumor initiation and progression and the potential for targeting anti-oxidants for therapeutic intervention. In addition, I will describe studies from our laboratory using 3-dimensional culture systems to model early events in breast cancer which have highlighted the critical role of oxidative stress in eliminating aberrantly proliferating breast epithelial cells, as well as the role of endogenous anti-oxidants in promoting proliferation and survival of pre-malignant cells. I will also discuss studies providing evidence for an unconventional mechanism whereby cancer cells co-opt the ROS-activated neuronal Ca2+-permeable TRPA1 channel in order to adapt to oxidative environments. Citation Format: Brugge J. Oxidative stress responses in cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr ES6-1.","PeriodicalId":224797,"journal":{"name":"Invited Speaker Abstracts","volume":"16 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"117102868","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":"Abstract ES12-3: BRCA 1/2/3 and p53 in replication fork stability","authors":"K. Schlacher","doi":"10.1158/1538-7445.SABCS18-ES12-3","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-ES12-3","url":null,"abstract":"","PeriodicalId":224797,"journal":{"name":"Invited Speaker Abstracts","volume":"57 12","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114023724","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":"Abstract ES1-2: Early HER2-positive breast cancer: Doing more and less","authors":"L. Carey","doi":"10.1158/1538-7445.SABCS18-ES1-2","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-ES1-2","url":null,"abstract":"","PeriodicalId":224797,"journal":{"name":"Invited Speaker Abstracts","volume":"166 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127448572","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":"Abstract TS3-2: Modulation of anti-tumor immunity using CDK4/6 inhibitors","authors":"S. Goel","doi":"10.1158/1538-7445.SABCS18-TS3-2","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-TS3-2","url":null,"abstract":"","PeriodicalId":224797,"journal":{"name":"Invited Speaker Abstracts","volume":"79 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125002127","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":"Abstract MS1-3: Artificial intelligence to optimize the accuracy and predictiveness of breast cancer pathology","authors":"A. Beck","doi":"10.1158/1538-7445.SABCS18-MS1-3","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-MS1-3","url":null,"abstract":"","PeriodicalId":224797,"journal":{"name":"Invited Speaker Abstracts","volume":"9 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131972785","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}