MOLECULAR THERAPEUTICS ? ABSTRACT The mission of the Molecular Therapeutics (MT) Program is to translate laboratory findings to the clinic and to facilitate collaborations between basic and clinical scientists, to improve the lives of patients with cancer by identifying new molecules, targets, and strategies for treating cancer. This highly interactive Program includes 50 members from 11 departments and 4 schools at Wayne State University and the Karmanos Cancer Institute (KCI) Network and $3,031,514 in peer reviewed, cancer-related funding, of which $971,206 is from the NCI. Additionally, industry-sponsored clinical trial funding is $29,599,781. Program membership includes a cross section of laboratory-based and clinical investigators in the KCI who interact through programmatic activities and collaborate on research grants and investigator-initiated clinical trials. The scientific themes of the MT Program are to: 1) identify and validate novel therapeutics, targets and pathways for selective tumor targeting; 2) identify cellular/molecular determinants and biomarkers of tumor response; and 3) validate effectiveness of new agents in interventional treatment trials. The MT Program focuses on new approaches for treating cancer, ranging from drug discovery to mechanism-based efforts emphasizing mechanisms-of-action of novel tumor-targeted and standard agents and critical signaling pathways, all with the goal of clinical translation. The interests of MT members include tumor metabolism, nuclear transporters, transcriptional targets, and signaling pathways, and extend to the impact of therapy on tumor-infiltrating immune cells. Biomarker research includes pharmacokinetics and pharmacodynamics, cellular and molecular biomarkers and molecular/genetic profiles predictive of responses to therapy and/or that lead to actionable therapies. A particular emphasis is on biomarkers relevant to cancer disparities between African American and white patients as treatment targets and for personalized treatment trials. Research in the MT Program draws from our nationally/internationally recognized clinical trials program at KCI, which employs tumor profiling (including genomic profiling) to facilitate enrollment on phase I and early phase II trials and to identify patients most likely to respond to particular treatments. Phase II clinical trials draw from basic laboratory findings, culminating in investigator-initiated clinical trials. MT members lead phase III trials, often working with multi-center teams and cooperative groups. MT Program members study all major cancer types including those that occur at high incidence in the KCI catchment area. These initiatives have helped define cancer health disparities in our catchment area, identify racial differences in tumor biology, and led to enrollment of large numbers of African Americans in clinical trials. The overriding goal of the MT Program is to conduct and deliver patient-centered cancer research and treatment to benefit patients in the catchment area. MT Program members extensively collaborate with members of the MI, TBM, and PSDR Programs at KCI. Of the 935 manuscripts published between December 2015 and November 2019, 34% and 32% were intra- and inter-programmatic, respectively, and 62% were multi-institutional collaborations.
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