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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Zhang, Sai; Zhou, Jingtian; Hu, Hailin et al. (2016) A deep learning framework for modeling structural features of RNA-binding protein targets. Nucleic Acids Res 44:e32
Macura, Sherrill L; Lathrop, Melissa J; Gui, Jiang et al. (2016) Blocking CXCL9 Decreases HIV-1 Replication and Enhances the Activity of Prophylactic Antiretrovirals in Human Cervical Tissues. J Acquir Immune Defic Syndr 71:474-82
Whipple, Chery A; Boni, Andrea; Fisher, Jan L et al. (2016) The mitogen-activated protein kinase pathway plays a critical role in regulating immunological properties of BRAF mutant cutaneous melanoma cells. Melanoma Res 26:223-35
Sargent, Jennifer L; Li, Zhenghui; Aliprantis, Antonios O et al. (2016) Identification of Optimal Mouse Models of Systemic Sclerosis by Interspecies Comparative Genomics. Arthritis Rheumatol 68:2003-15
Hill, Courtney A; Beach, Michael; Smith, Mark C et al. (2016) Incidence of and Factors Associated With Hypogeusia in Healthy Children. JAMA Otolaryngol Head Neck Surg 142:229-33
Kim, Jung-Sik; He, Xiaoyuan; Orr, Bernardo et al. (2016) Intact Cohesion, Anaphase, and Chromosome Segregation in Human Cells Harboring Tumor-Derived Mutations in STAG2. PLoS Genet 12:e1005865
Yang, Wei; Hosford, Sarah R; Dillon, Lloye M et al. (2016) Strategically Timing Inhibition of Phosphatidylinositol 3-Kinase to Maximize Therapeutic Index in Estrogen Receptor Alpha-Positive, PIK3CA-Mutant Breast Cancer. Clin Cancer Res 22:2250-60
Beach, Michael L; Cohen, Daniel M; Gallagher, Susan M et al. (2016) Major Adverse Events and Relationship to Nil per Os Status in Pediatric Sedation/Anesthesia Outside the Operating Room: A Report of the Pediatric Sedation Research Consortium. Anesthesiology 124:80-8
Allaway, Robert J; Fischer, Dawn A; de Abreu, Francine B et al. (2016) Genomic characterization of patient-derived xenograft models established from fine needle aspirate biopsies of a primary pancreatic ductal adenocarcinoma and from patient-matched metastatic sites. Oncotarget 7:17087-102
Liu, Yu-Chen; Li, Jian-Rong; Sun, Chuan-Hu et al. (2016) CircNet: a database of circular RNAs derived from transcriptome sequencing data. Nucleic Acids Res 44:D209-15

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