The goal of the Molecular Therapeutics Program (MT) is to foster the exchange of ideas, cooperation, and collaboration leading to translation of basic research focused on the identification and development of novel therapeutics into clinical applications, and to use basic research to answer clinical questions related to improving the treatment of cancer. The MT Program provides a forum for discussion and advancement of new developments in target identification, drug discovery, and mechanisms of drug action, and for translating these approaches into novel correlative and therapeutic clinical trials. The Program currently has 27 members from 7 departments and $8.2 millon in total funding, of which almost $4 million (61%) is from the NCI. The productivity over the past 5 years exceeds 240 papers, including 16% intra-program and 26% interprogram collaborative publications. Eighteen Program faculty participated in intra-program and 18 in interprogram collaborations, providing strong evidence of a highly interactive research program. Recent programmatic highlights include evidence for the role of the fatty acid synthase pathway as an independent marker of breast cancer progression, and the recognition that it can be targeted to suppress tumor growth. Other molecular targets under investigation include proteins in the Hedgehog signaling pathway, which is frequently activated in non-small cell lung cancer. New agents such as novel proteasome inhibitors and suppressors of the anti-apoptotic proteins Mcl-1 and Bcl-2 are under investigation, with the expectation of bringing these drugs to clinical trial at Morris Cotton Cancer Center. Novel treatment strategies developed in the MT Program that have been translated into Phase I clinical trials include the combination of cisplatin plus the Chk1 inhibitor UCN-01. In is study serial tumor biopsies were used to monitor biological activity in tumor tissue. Other investigators have developed novel technologies and complementary approaches to define predictive markers and therapeutic strategies, and an important goal of the MT Program is to test these ideas in correlative and therapeutic clinical trials at the NCCC. Also worthy of particular notice is a series of Phase I and II clinical trials in pancreatic cancer using chemoradiation in the neoadjuvant setting that has identified a promising treatment approach in this highly aggressive disease and demonstrates the Program's impact on disease outcome in cancer patients.

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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Dartmouth College
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Emond, Jennifer A; Tovar, Alison; Li, Zhigang et al. (2017) FTO genotype and weight status among preadolescents: Assessing the mediating effects of obesogenic appetitive traits. Appetite 117:321-329
Rapuano, Kristina M; Zieselman, Amanda L; Kelley, William M et al. (2017) Genetic risk for obesity predicts nucleus accumbens size and responsivity to real-world food cues. Proc Natl Acad Sci U S A 114:160-165
Carroll, A M; Cheng, R; Collie-Duguid, E S R et al. (2017) Fine-mapping of genes determining extrafusal fiber properties in murine soleus muscle. Physiol Genomics 49:141-150
Fang, Jun; Jia, Jinping; Makowski, Matthew et al. (2017) Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148. Nat Commun 8:15034
Pan, Yongchu; Liu, Hongliang; Wang, Yanru et al. (2017) Associations between genetic variants in mRNA splicing-related genes and risk of lung cancer: a pathway-based analysis from published GWASs. Sci Rep 7:44634
Rothwell, Simon; Cooper, Robert G; Lundberg, Ingrid E et al. (2017) Immune-Array Analysis in Sporadic Inclusion Body Myositis Reveals HLA-DRB1 Amino Acid Heterogeneity Across the Myositis Spectrum. Arthritis Rheumatol 69:1090-1099
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Melin, Beatrice S; Barnholtz-Sloan, Jill S; Wrensch, Margaret R et al. (2017) Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors. Nat Genet 49:789-794
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