# Investigation of heterogeneity in cancer cell proliferation.

> **NIH NIH F30** · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 · $51,752

## Abstract

Project Summary/Abstract
Lung adenocarcinoma is a complex disease with high prevalence and mortality. The low survival rate is worsened
by the long-term ineffectiveness of many cancer therapeutics, which eliminate most but not all of the cancer cells
in a tumor. Cellular phenotypic diversity is an important feature of cancer for the fields of basic biology and
medicine, but the mechanisms by which tumors establish and maintain this diversity is poorly understood. One
key aspect of tumor phenotypic diversity is proliferative heterogeneity: the presence of cancer cells that exist in
proliferative states ranging from quiescence to persistent cell division. The Wnt pathway is a potentially important
driver of proliferative heterogeneity, as it is central to the maintenance of a highly proliferative, cancer stem cell-
like state in lung adenocarcinoma. To interrogate proliferative heterogeneity in an unbiased manner, we have
established a novel genetically engineered mouse model of lung adenocarcinoma that enable us to identify
different tumor subpopulations based on proliferative state. We will use this mouse model to isolate highly
proliferative and persistently quiescent cancer cells, which we will then interrogate functionally and
transcriptionally. In these experiments we seek to identify the impact of a cell’s proliferative state on its
tumorigenic capacity (Aim 1). We will also characterize the mechanisms by which distinct proliferative states are
established and maintained. In particular, we will focus on the Wnt pathway to identify the role of individual Wnt
ligands in driving distinct proliferative states. The goal of these experiments is to determine the impact of targeting
Wnt signaling on specific proliferative states and to identify additional cell states with robust growth potential
(Aim 2). Lung cancer has a poor prognosis, but basic science research that improves the understanding of lung
tumor heterogeneity can lead to significant advancements in how patients are treated. Further elucidating the
phenotypic diversity that causes disease relapses may advance our ability to control tumor behavior and increase
the ability of existing cancer treatments to fully eradicate the disease through elimination of resistant cell states.

## Key facts

- **NIH application ID:** 10434832
- **Project number:** 5F30CA254120-03
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Stefan Ross Torborg
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $51,752
- **Award type:** 5
- **Project period:** 2020-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10434832

## Citation

> US National Institutes of Health, RePORTER application 10434832, Investigation of heterogeneity in cancer cell proliferation. (5F30CA254120-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10434832. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*