# Triggering a New Cancer Cell Death Mechanism in Sarcoma

> **NIH NIH R01** · STANFORD UNIVERSITY · 2023 · $458,362

## Abstract

Project Abstract
Lethal small molecules are powerful tools to discover and characterize new cell death
mechanisms that may be useful for cancer treatment. Using small molecules, we have identified
an unconventional form of non-apoptotic cell death that is distinct from apoptosis, ferroptosis,
and other known forms of cell death. This lethal mechanism requires protein palmitoylation and
involves the disruption of protein trafficking. In this research we propose to test the role of lipid
metabolic enzymes that may positively or negatively regulate palmoptosis. One Aim of this
research will focus on the lipid metabolic enzyme TECR (trans-2,3-enoyl-CoA reductase). We
will test the hypothesis that TECR synthesizes palmitate that is used by protein palmitoylation
enzymes to drive cell death via altered protein trafficking. A second Aim of this research will test
the hypothesis that cell death is triggered by the disruption of phosphatidylcholine metabolism,
which alters protein trafficking. A third Aim of this research will test the hypothesis that this new
cell death mechanism can be activated in genetically engineered mouse models of cancer by a
clinical drug candidate. While this cell death mechanism can be activated in diverse cancers, a
major focus of the proposed studies is on sarcoma, which is highly sensitive to this lethal
mechanism and for which new treatments are urgently needed. Together, these studies will
define a new form of cell death and associated biochemical mechanisms that may be exploited
for the treatment of sarcoma and other cancers.

## Key facts

- **NIH application ID:** 10735740
- **Project number:** 1R01CA272485-01A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Scott Dixon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $458,362
- **Award type:** 1
- **Project period:** 2023-06-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10735740

## Citation

> US National Institutes of Health, RePORTER application 10735740, Triggering a New Cancer Cell Death Mechanism in Sarcoma (1R01CA272485-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10735740. Licensed CC0.

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