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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Shee, Kevin; Jiang, Amanda; Varn, Frederick S et al. (2018) Cytokine sensitivity screening highlights BMP4 pathway signaling as a therapeutic opportunity in ER+ breast cancer. FASEB J :fj201801241R
Rodriguez-Garcia, Marta; Fortier, Jared M; Barr, Fiona D et al. (2018) Aging impacts CD103+ CD8+ T cell presence and induction by dendritic cells in the genital tract. Aging Cell 17:e12733
Shajani-Yi, Zahra; de Abreu, Francine B; Peterson, Jason D et al. (2018) Frequency of Somatic TP53 Mutations in Combination with Known Pathogenic Mutations in Colon Adenocarcinoma, Non-Small Cell Lung Carcinoma, and Gliomas as Identified by Next-Generation Sequencing. Neoplasia 20:256-262
Szczepiorkowski, Zbigniew M; Burnett, Christine A; Dumont, Larry J et al. (2018) Apheresis buffy coat collection without photoactivation has no effect on apoptosis, cell proliferation, and total viability of mononuclear cells collected using photopheresis systems. Transfusion 58:943-950
Bossé, Yohan; Amos, Christopher I (2018) A Decade of GWAS Results in Lung Cancer. Cancer Epidemiol Biomarkers Prev 27:363-379
Pande, Mala; Joon, Aron; Brewster, Abenaa M et al. (2018) Genetic susceptibility markers for a breast-colorectal cancer phenotype: Exploratory results from genome-wide association studies. PLoS One 13:e0196245
Smith, T Jarrod; Sondermann, Holger; O'Toole, George A (2018) Co-opting the Lap System of Pseudomonas fluorescens To Reversibly Customize Bacterial Cell Surfaces. ACS Synth Biol 7:2612-2617
Gorlova, Olga Y; Li, Yafang; Gorlov, Ivan et al. (2018) Gene-level association analysis of systemic sclerosis: A comparison of African-Americans and White populations. PLoS One 13:e0189498
Schmit, Stephanie L; Edlund, Christopher K; Schumacher, Fredrick R et al. (2018) Novel Common Genetic Susceptibility Loci for Colorectal Cancer. J Natl Cancer Inst :
Cai, Yunliang; Wu, Shaoju; Zhao, Wei et al. (2018) Concussion classification via deep learning using whole-brain white matter fiber strains. PLoS One 13:e0197992

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