Theme 1: Identify and validate novel therapeutics, targets and pathways for selective tumor targeting

The MT Program is working to develop new therapeutic approaches for treating cancer. These include drug discovery ranging from traditional medicinal chemistry and rational drug design based on structural biology considerations, to high-throughput screening of chemical libraries to identify lead compounds for follow-up compound synthesis. Particular focus is on mechanisms-of-action of novel tumor-targeted and standard therapeutic agents, and targeting critical cellular pathways, all with the ultimate goal of clinical translation. The biological interests of MT members are diverse and include novel membrane transporters, nuclear transporters, transcriptional targets, signaling pathways, and tumor metabolism as examples.

Theme 1 Scientific Accomplishments 

Theme 2: Identify cellular/molecular determinants and biomarkers of tumor response

An important benchmark of translational cancer research involves clinically relevant biomarkers of treatment response or upon which to base therapy. Biomarker research is integral to the mission of the MT Program and is interwoven with both programmatic themes 1 and 3. Current topics of interest include pharmacokinetic and pharmacodynamic biomarkers, identification of established cellular and molecular biomarkers predictive of responses to therapy with both standard and targeted agents, and identification of genomic biomarkers and driver mutations which can lead to actionable therapies. The focus of biomarker research in the MT Program encompasses a variety of cancers with emphasis on molecular processes rather than anatomical classifications. An important emphasis is on biomarkers relevant to cancer disparities between African-American and Caucasian patients.

Theme 2 Scientific Accomplishments 

Validate clinical effectiveness of new agents in interventional treatment trials

An important strength of the MT Program is our nationally/internationally recognized clinical trials program which is developing and conducting novel clinical trials. Agents are typically studied by our Phase I team and our multidisciplinary tumor teams, such that promising agents can then be advanced to Phase II studies. Both Phase I and II clinical trials increasingly employ tumor profiling (including genomic profiling) to identify patients most likely to respond to particular treatments. Phase II clinical trials also draw from basic laboratory findings, culminating in investigator-initiated clinical trials strongly based on research initiated at Karmanos. MT members also lead a number of Phase III trials, often working with multi-center teams and cooperative groups. Investigators in other cancer center programs, notably Molecular Imaging (MI) and the Tumor Biology and Microenvironment (TBM) Programs, have worked closely with basic and clinical members in MT to test new therapies for cancer. MT Program members are working with the Population Sciences and Disparity Research (PSDR) Program to identify genomic biomarkers in the context of clinical trials and to explore the psychosocial consequences of chemotherapy for patients and families, and to improve clinical trials enrollment among minority populations. A particular strength of our clinical trials program is our focus on cancer disparities, as 27.4% of patients enrolled on clinical trials at Karmanos are African-American.

Theme 3 Scientific Accomplishments 

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