# Arizona Cancer and Evolution Center (ACE)

> **NIH NIH U54** · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · 2020 · $1,747,581

## Abstract

Overall Project Summary/Abstract
Cancer is an evolutionary and ecological phenomenon driven by the fundamental forces of evolution:
mutations, natural selection and genetic drift. It provides a classic example of multi-level selection. At the level
of individual cancer cells, selection favors neoplastic proliferation; at the level of the host organism, selection
favors cancer suppression. A full understanding of cancer hinges on an appreciation of this fundamental
tension. Regulatory mechanisms at the organismal level determine evolutionary parameters at the cell level
such as the somatic mutation rate and response to DNA damage. Cancer circumvents those constraints and
changes the parameters of cell-level evolution, leading to malignancy and eventual host death. Thus,
organismal and cell-level evolution feedback upon each other. To paraphrase Dobzhansky, nothing in cancer
biology makes sense except in the light of evolution. This opens an opportunity. We may apply evolutionary
and ecological theory to neoplastic progression and response to therapy. The mission of the Arizona Cancer
and Evolution Center (ACE) is to advance our fundamental understanding of cancer and its clinical
management through the development and application of evolutionary and ecological models to cancer
biology. This mission spans scales from the evolution of cancer suppression mechanisms and cancer
susceptibility across species (Project 1) down to the evolution of normal somatic cells (Project 2) and
populations of cancer cells (Project 3). Project 1 will develop models of organismal evolution to predict cancer
rates and cancer defenses across species. We will test those predictions using veterinary databases of cancer
incidence in over 1,900 animal species, and examine the genomes of 57 mammalian species for evidence of
adaptations to the selective pressure of cancer. In addition, Project 2 will test Project 1's model predictions of
cancer defenses in primary cells from those same 57 mammalian species. Project 2 will also measure the
fundamental forces of evolution in normal colonic and small intestine tissue from humans, mice and elephants
to address a basic but poorly understood property of cancer: tissue-level differences in cancer susceptibility.
Project 3 will develop novel evolutionary and ecological indices, based on models of cell-level evolution in
neoplasms from Project 1, to predict long term therapeutic response and patient survival in stage 2&3, chemo-
naïve colorectal cancers. These indices will provide, for the first time, a classification system that the
community can use to draw distinctions between tumors with different evolutionary dynamics, and thereby
provide a foundation for the clinical management of this evolving disease. ACE will support the Cancer
Systems Biology Consortium and the growing field of evolution and cancer by providing data, analytical tools,
models, workshops, and tutorials to facilitate the use of those resources.

## Key facts

- **NIH application ID:** 9900751
- **Project number:** 5U54CA217376-03
- **Recipient organization:** ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
- **Principal Investigator:** Carlo Maley
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,747,581
- **Award type:** 5
- **Project period:** 2018-04-12 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900751

## Citation

> US National Institutes of Health, RePORTER application 9900751, Arizona Cancer and Evolution Center (ACE) (5U54CA217376-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9900751. Licensed CC0.

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