Project Details
Description
EXPERIMENTAL THERAPEUTICS PROGRAM PROJECT SUMMARY
The Experimental Therapeutics (ET) Program contributes to more effective treatment of neoplastic diseases
through a spectrum of basic and translational research. The Aims are to 1) define cellular pathways involved in
survival and proliferation in order to improve understanding of response to established treatments and identify
new therapeutic targets; 2) elucidate biological, biochemical, and pharmacological aspects of the action of
novel anti-cancer agents and identify biochemical properties that contribute to tumor cell resistance;
3) evaluate potential genetic and genomic contributions to efficacy and toxicity of anticancer treatments; and
4) conduct early phase clinical trials, based on research in this Program and others, with hand off to disease-
specific clinical Programs for phase II testing after initial assessment of safety, pharmacokinetics,
pharmacogenetics, and biological effects in the clinical setting. The Program is jointly led by Zhenkun Lou,
PhD, Scott Kaufmann, MD, PhD, and Alex Adjei, MD, PhD, who have expertise in DNA repair, cellular
signaling, cellular pharmacology, and the conduct of early phase clinical trials. The ET Program has 46
members from 13 departments and divisions, with total direct funding of $12.6M ($8M peer-reviewed, with 88%
from NCI). Since the last competitive renewal, the Program has generated 777 publications (129 published in
journals with impact factor ≥10, 42 with impact factor ≥20) with 21% and 50% of these publications reflecting
intra- and interprogrammatic collaborations, respectively. Notable accomplishments include 1) the
demonstration that protein kinase Cι transforms lung adenocarcinoma through the hedgehog pathway and
ovarian cancer through the Hippo/YAP pathway; 2) preclinical work showing that CDK4/6 inhibitors alter the
epithelial-to-mesenchymal transition and metastasis of breast cancer cells, leading to a CDK4/6
inhibitor/aromatase inhibitor phase II trial in the Women's Cancer Program; 3) demonstration that ZNF423
regulates BRCA1 expression, and allelic variation in this pathway affects the chemopreventive efficacy of
tamoxifen; and 4) completion of phase I trials of endoxifen and PARP inhibitors as well as initiation of early
phase trials of ATR inhibitors. The Program makes extensive use of Shared Resources, especially the
Microscopy and Cell Analysis, Proteomics, Pathology Research, Genome Analysis, Pharmacology, and
Pharmacy facilities as well as the Clinical Research Office. The Program adds value to the Mayo Clinic Cancer
Center (MCCC) by i) bringing together investigators with a shared emphasis on the preclinical and early clinical
study of small molecule therapeutics, alone or in conjunction with immuno-oncology agents, and ii) serving as
a resource for early phase clinical trials for MCCC Programs. Future goals of the program include 1) further
preclinical work on deubiquitinases and their inhibitors as modulators of DNA repair pathways, 2) expansion of
our emphasis on metabolic targets in cancer, and 3) translation of ongoing work on DNA repair, metabolic
targets, and chemotherapy/immunotherapy combinations into novel clinical trials.
Status | Finished |
---|---|
Effective start/end date | 3/1/19 → 2/29/24 |
Funding
- National Cancer Institute: $98,245.00
- National Cancer Institute: $100,687.00
- National Cancer Institute: $81,108.00
- National Cancer Institute: $98,245.00
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