Project Summary
The Early Phase Clinical Cancer Prevention Consortium proposes to develop, implement, and complete early
clinical trials targeting cellular stemness. Most cancers display a hierarchical organization that is driven by a
population of cells that are “stem-like”. Inflammatory stress drives increased stem cell self-renewal across
different organ sites. The sources of chronic inflammatory stess include obesity, explosures (alcohol, chemicals),
infectious agents, microbial dysbiosis, and genetic polymorphisms. Of these, the obesity-associated metabolic
syndrome associated is reaching epidemic proportions. This consortium addresses the overarching hypothesis
that inflammatory-induced shifts in the tissue stromal environment increase stem cell self-renewal and enhance
epithelial mesenchymal transformation. These shifts can be reversed or dampened by biomarker driven dosing
of clinical preventive agents, either alone or in combination. We select agents that target the adverse metabolic
milieu resulting from inflammatory exposures and driving stem cell proliferation. The Consortium proposes the
following aims: 1. To develop and submit at least three proposals each year for early phase trials for the
prevention of obesity-related cancers (colon, lower esophagus, breast, prostate, bladder); 2. To conduct 1 to 3
early phase cancer prevention trials per year within the fiscal capacity of the grant that include evaluating
translational endpoints in biospecimens, asssessing the pharmacokinetics and pharmacodynamics, and
obtaining mechanistic proof-of-principle data; and 3. To manage all aspects of study operations while complying
with all applicable rules and regulations for the conduct of clinical trials. The University of Michigan Rogel Cancer
Center is the lead organization of a consortium consisting of 9 institutions of which all are within NCI Core Funded
Cancer Centers. The intellectual diversity and strong academic accomplishement of our consortium permits
deep intellectual engagement combined with the experienced logistics of participant recruitment and retention,
and the infrastructure support available in NCI supported cancer centers. We have established processes to
ensure rapid turn-around of letters of intent and protocol documents, uniform sample handling, management and
shipment, and rapid analysis of biosamples. The Consortium will collaborate with other the CP-CTNet consortia
to create synergies of science and resources, enabling paradigm shifts that rapidly test and prioritize agents for
Phase III trials conducted in individuals at increased risk of cancer.