The overall goal of project 4 is to develop novel approaches distinct from ATP mimetics to overcome resistance to BRAF inhibitors for treatment of melanoma. This project will focus on two mechanisms of resistance;BRAF dimerization leading to paradoxical MAPK activation and STATS activation which is downstream of a number of parallel signaling pathways that are activated in BRAF inhibitor resistant cells as well as in BRAF^'

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA114046-06
Application #
8604781
Study Section
Special Emphasis Panel (ZCA1-RPRB-2 (M1))
Project Start
2005-04-01
Project End
2018-08-31
Budget Start
2013-09-25
Budget End
2014-08-31
Support Year
6
Fiscal Year
2013
Total Cost
$425,498
Indirect Cost
$136,139
Name
Wistar Institute
Department
Type
DUNS #
075524595
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Webster, Marie R; Xu, Mai; Kinzler, Kathryn A et al. (2015) Wnt5A promotes an adaptive, senescent-like stress response, while continuing to drive invasion in melanoma cells. Pigment Cell Melanoma Res 28:184-95
Leu, Julia I-Ju; Zhang, Pingfeng; Murphy, Maureen E et al. (2014) Structural basis for the inhibition of HSP70 and DnaK chaperones by small-molecule targeting of a C-terminal allosteric pocket. ACS Chem Biol 9:2508-16
Vultur, A; Villanueva, J; Krepler, C et al. (2014) MEK inhibition affects STAT3 signaling and invasion in human melanoma cell lines. Oncogene 33:1850-61
Streib, Manuel; Kraling, Katja; Richter, Kristin et al. (2014) An organometallic inhibitor for the human repair enzyme 7,8-dihydro-8-oxoguanosine triphosphatase. Angew Chem Int Ed Engl 53:305-9
Ma, Xiao-Hong; Piao, Sheng-Fu; Dey, Souvik et al. (2014) Targeting ER stress-induced autophagy overcomes BRAF inhibitor resistance in melanoma. J Clin Invest 124:1406-17
Zhang, Pingfeng; Leu, Julia I-Ju; Murphy, Maureen E et al. (2014) Crystal structure of the stress-inducible human heat shock protein 70 substrate-binding domain in complex with peptide substrate. PLoS One 9:e103518
Wang, Tao; Ge, Yingbin; Xiao, Min et al. (2014) SECTM1 produced by tumor cells attracts human monocytes via CD7-mediated activation of the PI3K pathway. J Invest Dermatol 134:1108-18
Malecka, Kimberly A; Fera, Daniela; Schultz, David C et al. (2014) Identification and characterization of small molecule human papillomavirus E6 inhibitors. ACS Chem Biol 9:1603-12
Licciulli, Silvia; Maksimoska, Jasna; Zhou, Chun et al. (2013) FRAX597, a small molecule inhibitor of the p21-activated kinases, inhibits tumorigenesis of neurofibromatosis type 2 (NF2)-associated Schwannomas. J Biol Chem 288:29105-14
Kastl, Anja; Dieckmann, Sandra; Wahler, Kathrin et al. (2013) Rhenium complexes with visible-light-induced anticancer activity. ChemMedChem 8:924-7

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