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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Hou, Huagang; Krishnamurthy Nemani, Venkata; Du, Gaixin et al. (2015) Monitoring oxygen levels in orthotopic human glioma xenograft following carbogen inhalation and chemotherapy by implantable resonator-based oximetry. Int J Cancer 136:1688-96
Gilbert-Diamond, Diane; Li, Zhigang; Adachi-Mejia, Anna M et al. (2014) Association of a television in the bedroom with increased adiposity gain in a nationally representative sample of children and adolescents. JAMA Pediatr 168:427-34
Sheen, Mee Rie; Lizotte, Patrick H; Toraya-Brown, Seiko et al. (2014) Stimulating antitumor immunity with nanoparticles. Wiley Interdiscip Rev Nanomed Nanobiotechnol 6:496-505
Koestler, Devin C; Li, Jing; Baron, John A et al. (2014) Distinct patterns of DNA methylation in conventional adenomas involving the right and left colon. Mod Pathol 27:145-55
Soderquist, Ryan; Pletnev, Alexandre A; Danilov, Alexey V et al. (2014) The putative BH3 mimetic S1 sensitizes leukemia to ABT-737 by increasing reactive oxygen species, inducing endoplasmic reticulum stress, and upregulating the BH3-only protein NOXA. Apoptosis 19:201-9
Tang, Hongwei; Wei, Peng; Duell, Eric J et al. (2014) Axonal guidance signaling pathway interacting with smoking in modifying the risk of pancreatic cancer: a gene- and pathway-based interaction analysis of GWAS data. Carcinogenesis 35:1039-45
Toraya-Brown, Seiko; Sheen, Mee Rie; Zhang, Peisheng et al. (2014) Local hyperthermia treatment of tumors induces CD8(+) T cell-mediated resistance against distal and secondary tumors. Nanomedicine 10:1273-85
O'Connor, Megan A; Green, William R (2014) Use of IRF-3 and/or IRF-7 knockout mice to study viral pathogenesis: lessons from a murine retrovirus-induced AIDS model. J Virol 88:2349-53
Tichauer, Kenneth M; Deharvengt, Sophie J; Samkoe, Kimberley S et al. (2014) Tumor endothelial marker imaging in melanomas using dual-tracer fluorescence molecular imaging. Mol Imaging Biol 16:372-82
Busch, Alexander M; Galimberti, Fabrizio; Nehls, Kristen E et al. (2014) All-trans-retinoic acid antagonizes the Hedgehog pathway by inducing patched. Cancer Biol Ther 15:463-72

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