The Signal Transduction (ST) Research Program promotes studies aimed at understanding of signal transduction pathways in carcinogenesis and cancer progression. In the long run, this will facilitate development of effective cancer therapeutics and optimal matching of targeted drugs to individual patients for maximal therapeutic impact The Signal Transduction Research Program was established in the previous cycle of this CCSG based on two major premises. First, the majority of human cancers are driven by dysregulation of cellular pathways that normally link hormone-dependent signaling to fundamental cellular processes relevant to cancer including regulation of cell division, protection from apoptosis, tumor angiogenesis, lineage restrictions, and changes associated with cancer progression. Second, signal transduction molecules, including peptide growth factors, receptor kinases, non-receptor kinases, and components of pathways that they regulate, have emerged as important targets for new cancer therapies. The portfolio of effective new cancer therapies that attack oncogenic signaling products and their subservient pathways has expanded to encompass dozens of US FDA-approved pharmaceuticals, with many more in the clinical developmental pipeline. These drugs, when, employed with patient selection based on genetic or functional criteria, have great impact, but as yet are only appropriate for a minority of cancer patients. Moreover, with increased experience in the clinic, a major practical issue has emerged: the rapid development of resistance to these agents, even in patients who initially responded dramatically. Hence, an important new area of investigation in the ST Research Program is the mechanisms of drug resistance, and the means to anticipate and defeat them. The 31 ST program members are drawn from 14 departments at Yale College and Yale Medical School. They include faculty investigating all aspects of signal transduction research related to cancer, including work on receptor signaling mechanisms, signaling pathways, cytoskeleton, cell polarity, intracellular protein trafficking, and integrated signaling networks. Recruitment of six new faculty with research programs centered on cancer biology has increased cancer focus. Since the last CCSG cycle, ST program members have published 412 (2006-2012) cancer related papers, of which 24 (6%) were intra-programmatic and 105 (25%) inter-programmatic. The total cancer research funding of the ST Program is $6.7M annual direct costs ($10.4M total costs, of which $8.4M is peer-reviewed, and $3.7 M NCI-funded).

National Institute of Health (NIH)
National Cancer Institute (NCI)
Center Core Grants (P30)
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Subcommittee G - Education (NCI)
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Yale University
New Haven
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Ols, Michelle L; Cullen, Jaime L; Turqueti-Neves, Adriana et al. (2016) Dendritic Cells Regulate Extrafollicular Autoreactive B Cells via T Cells Expressing Fas and Fas Ligand. Immunity 45:1052-1065
Gale, Molly; Sayegh, Joyce; Cao, Jian et al. (2016) Screen-identified selective inhibitor of lysine demethylase 5A blocks cancer cell growth and drug resistance. Oncotarget 7:39931-39944
Ducker, Gregory S; Chen, Li; Morscher, Raphael J et al. (2016) Reversal of Cytosolic One-Carbon Flux Compensates for Loss of the Mitochondrial Folate Pathway. Cell Metab 23:1140-53
Adams, Brian D; Wali, Vikram B; Cheng, Christopher J et al. (2016) miR-34a Silences c-SRC to Attenuate Tumor Growth in Triple-Negative Breast Cancer. Cancer Res 76:927-39
Santin, Alessandro D; Bellone, Stefania; Buza, Natalia et al. (2016) Regression of Chemotherapy-Resistant Polymerase ε (POLE) Ultra-Mutated and MSH6 Hyper-Mutated Endometrial Tumors with Nivolumab. Clin Cancer Res 22:5682-5687
de Haydu, Christopher; Black, Jonathan D; Schwab, Carlton L et al. (2016) An update on the current pharmacotherapy for endometrial cancer. Expert Opin Pharmacother 17:489-99
Hollander, Lindsay; Guo, Xiaojia; Velazquez, Heino et al. (2016) Renalase Expression by Melanoma and Tumor-Associated Macrophages Promotes Tumor Growth through a STAT3-Mediated Mechanism. Cancer Res 76:3884-94
Zhao, Siming; Bellone, Stefania; Lopez, Salvatore et al. (2016) Mutational landscape of uterine and ovarian carcinosarcomas implicates histone genes in epithelial-mesenchymal transition. Proc Natl Acad Sci U S A 113:12238-12243
Park, Sin-Aye; Lee, Jong Woo; Herbst, Roy S et al. (2016) GSK-3α Is a Novel Target of CREB and CREB-GSK-3α Signaling Participates in Cell Viability in Lung Cancer. PLoS One 11:e0153075
Stein, Stacey M; James, Edward S; Deng, Yanhong et al. (2016) Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer. Br J Cancer 114:737-43

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