BHAVANI KRISHNAN Reprogramming of the Kinome to enhance Mammalian Target of Rapamycin (mTOR) Inhibitor responsiveness in Renal Cell Carcinoma

Project: Research project

Description

Innovation: In this proposal we combine the innovative MIB-MS assay that allows the ability to measure activation state of the kinome and enriches for lower abundance kinases by quantitative proteomics; and a cohort of RCC PDX tumors. Combining the determination of kinase activity by MIB-MS with the PDX model strengthens the translational and pre-clinical value of the identified candidate kinases.
Impact: mTOR inhibitors are FDA approved drugs, this coupled with the fact that over 130 kinase-specific inhibitors are currently in Phase 1-3 clinical trials should allow the expedited clinical implementation of identified combinations in comparison to new drug development. An added benefit of this study is the prospect that results here may also be able to positively impact the progress of clinical drug development of other cancers (trials are currently ongoing in lung, breast and prostate) as well. Taken together this proposal would ultimately not only improve mTOR inhibition outcome and survival but also provide a reasonable quality of life to patients with RCC.
StatusFinished
Effective start/end date9/15/139/14/16

Funding

  • Department of Defense (DOD)

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Sirolimus
Renal Cell Carcinoma
Phosphotransferases
Pharmaceutical Preparations
Phase III Clinical Trials
Clinical Trials, Phase I
Proteomics
Prostate
Neoplasms
Breast
Quality of Life
Lung
Survival