SIGNAL TRANSDUCTION RESEARCH PROGRAM PROGRAM CODE: ST PROJECT SUMMARY/ABSTRACT The Signal Transduction (ST) Research Program harnesses research talent across YCC to understand fundamentals of key pathways that drive carcinogenesis and cancer progression, with the goal of enabling development and improvement of effective targeted cancer therapeutics. The ST Program was established in 2005 with two major premises. First, most human cancers are driven by dysregulation of cellular pathways that normally link growth factor-dependent signaling to cellular processes relevant to cancer, including regulation of cell division, protection from apoptosis, tumor angiogenesis, lineage restrictions, and cancer progression. Second, molecules involved in signal transduction networks ? including growth factors, receptor kinases, non- receptor kinases, and components that they regulate ? have emerged as important targets for cancer therapies. The portfolio of effective FDA-approved cancer therapies that attack oncogenic signaling proteins is extensive, and now includes third-generation agents that have been refined based on clinical experience. New categories of agents, including PARP inhibitors and CDK inhibitors, have more recently been shown to be effective and are now in routine clinical practice. Immunotherapy has transformed the cancer treatment landscape; nonetheless, current checkpoint inhibitors benefit only a minority of patients ? creating an urgent need to define relevant signaling pathways that can be targeted alongside checkpoint blockade to overcome both primary and acquired resistance. Challenges remain for all signaling-targeted therapies, including intrinsic and treatment-selected resistance and failure to successfully target RAS. ST takes full advantage of cutting- edge technologies to identify critical drivers of initiation and progression of human cancers, as well as their response to therapy ? bringing together leading investigators across the spectrum of cancer research to advance fundamental understanding of cancer signaling and overcome treatment challenges. The Program leverages a variety of mechanisms to build new initiatives and research areas, including focused research meetings, pilot funding, member education, and matchmaking collaborations. The 38 ST program members come from 12 departments in 3 Schools. Members investigate all aspects of signal transduction research related to cancer, including receptor signaling mechanisms, signaling pathways, cytoskeleton, cell polarity, intracellular protein trafficking, and integrated signaling networks. Recruitment of 10 new faculty with research programs centered on cancer signaling and translation, and pruning of less cancer-oriented faculty has increased cancer focus. Since the last CCSG cycle, ST members published 546 (July 1, 2012 - June 1, 2017) cancer-related papers (11% intra-programmatic, and 32% inter-programmatic). Total ST cancer research funding is $15.8M (direct), of which $9.3M is peer-reviewed, and $3.9M NCI-funded. This represents a more than 2-fold increase in overall funding, an 80% increase in peer-reviewed funding and a 71% increase in NCI funding relative to the last submission in 2012. !

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA016359-41
Application #
9989601
Study Section
Subcommittee I - Transistion to Independence (NCI)
Project Start
Project End
Budget Start
2020-08-01
Budget End
2021-07-31
Support Year
41
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Yale University
Department
Type
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Jagannath, Sundar; Laubach, Jacob; Wong, Ellice et al. (2018) Elotuzumab monotherapy in patients with smouldering multiple myeloma: a phase 2 study. Br J Haematol 182:495-503
Liu, Xiaoni; Zhang, Shang-Min; McGeary, Meaghan K et al. (2018) KDM5B Promotes Drug Resistance by Regulating Melanoma Propagating Cell Subpopulations. Mol Cancer Ther :
Chae, Wook-Jin; Bothwell, Alfred L M (2018) Therapeutic Potential of Gene-Modified Regulatory T Cells: From Bench to Bedside. Front Immunol 9:303
Kim, Hanseul; Keum, NaNa; Giovannucci, Edward L et al. (2018) Garlic intake and gastric cancer risk: Results from two large prospective US cohort studies. Int J Cancer 143:1047-1053
Sarma, Elizabeth A; Kawachi, Ichiro; Poole, Elizabeth M et al. (2018) Social integration and survival after diagnosis of colorectal cancer. Cancer 124:833-840
Hartman, Douglas J; Ahmad, Fahad; Ferris, Robert L et al. (2018) Utility of CD8 score by automated quantitative image analysis in head and neck squamous cell carcinoma. Oral Oncol 86:278-287
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

Showing the most recent 10 out of 675 publications