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Convergence Cancer Evolution

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The SU2C– National Science Foundation – V Foundation Cancer Evolution Convergence Translational Research Team

Team Leader

  • Ross Levine, MD

    Team Leader
    Member, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
    + Full Bio

About This Team’s Research

The last two decades have seen the development of increasingly effective cancer therapies that target different facets of transformed cells, including aberrant proliferation/survival, immune evasion, hyper-activated signaling pathways and dysregulated transcriptional programs.  In a subset of cancers, including acute myeloid leukemia (AML) and non-small cell lung cancer with activating EGFR (epidermal growth factor receptor) mutations, these therapies lead to dramatic clinical responses in a significant proportion of patients.  However, in the majority of AML and EGFR mutant lung cancer patients who respond to anti-cancer therapies, therapeutic relapse subsequently ensues, although often after a considerable interval, such that these responses do not lead to long-term cures.  We propose to investigate the process of response to treatment, the basis for persistence of a subset of cells during clinical response, and the mechanisms driving subsequent therapeutic relapse in these two tumor types.  This will involve combining genomic, transcriptional, and phenotypic assays of tumors at the various stages of therapeutic response and resistance with mathematical modeling approaches to understand the evolution of drug resistance and to develop novel therapeutic strategies aimed to prevent the emergence of clinical resistance.  To do this we have assembled a collaborative team of cancer biologists, physician scientists with expertise in clinical oncology, and mathematical modelers.  The overall goal is to use studies of patient samples and accurate preclinical models to understand and to build quantitative dynamical models of the therapeutic response, and the emergence of clinical resistance.  Our integrative approach should lead to major advances in the understanding of the genetic and epigenetic evolution of cancer.  This will be critical to overcoming this intransient obstacle in the clinic.  The understanding gained from our studies will be used to develop and test innovative therapeutic strategies with informed, multimodality therapeutic regimens that include tumor-directed therapies and immunotherapy.  Our goal is to inform the use of combination therapies which are aimed to prevent therapeutic resistance and to maximize clinical response.

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