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).

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA016359-35
Application #
8755634
Study Section
Subcommittee G - Education (NCI)
Project Start
Project End
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
35
Fiscal Year
2014
Total Cost
$21,305
Indirect Cost
$8,509
Name
Yale University
Department
Type
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Chen, Ling; Azuma, Takeshi; Yu, Weiwei et al. (2018) B7-H1 maintains the polyclonal T cell response by protecting dendritic cells from cytotoxic T lymphocyte destruction. Proc Natl Acad Sci U S A 115:3126-3131
Zhang, Jinhua; Song, Kun; Wang, Jun et al. (2018) S100A4 blockage alleviates agonistic anti-CD137 antibody-induced liver pathology without disruption of antitumor immunity. Oncoimmunology 7:e1296996
Kelada, Olivia J; Decker, Roy H; Nath, Sameer K et al. (2018) High Single Doses of Radiation May Induce Elevated Levels of Hypoxia in Early-Stage Non-Small Cell Lung Cancer Tumors. Int J Radiat Oncol Biol Phys 102:174-183
Powles, Ryan L; Redmond, David; Sotiriou, Christos et al. (2018) Association of T-Cell Receptor Repertoire Use With Response to Combined Trastuzumab-Lapatinib Treatment of HER2-Positive Breast Cancer: Secondary Analysis of the NeoALTTO Randomized Clinical Trial. JAMA Oncol 4:e181564
Wang, Shi-Yi; Hsu, Sylvia H; Huang, Siwan et al. (2018) Regional Practice Patterns and Racial/Ethnic Differences in Intensity of End-of-Life Care. Health Serv Res 53:4291-4309
Gettinger, S N; Choi, J; Mani, N et al. (2018) A dormant TIL phenotype defines non-small cell lung carcinomas sensitive to immune checkpoint blockers. Nat Commun 9:3196
Liu, Huafeng; Li, Xin; Hu, Li et al. (2018) A crucial role of the PD-1H coinhibitory receptor in suppressing experimental asthma. Cell Mol Immunol 15:838-845
Altwerger, Gary; Bonazzoli, Elena; Bellone, Stefania et al. (2018) In Vitro and In Vivo Activity of IMGN853, an Antibody-Drug Conjugate Targeting Folate Receptor Alpha Linked to DM4, in Biologically Aggressive Endometrial Cancers. Mol Cancer Ther 17:1003-1011
Sanmamed, Miguel F; Chen, Lieping (2018) A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization. Cell 175:313-326
Gupta, Swati; Mani, Navin R; Carvajal-Hausdorf, Daniel E et al. (2018) Macrodissection prior to closed system RT-qPCR is not necessary for estrogen receptor and HER2 concordance with IHC/FISH in breast cancer. Lab Invest 98:1076-1083

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