# Targeting ALT-Cancer

> **NIH NIH R03** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $155,500

## Abstract

PROJECT SUMMARY
The long-term goal of the proposed project is to identify the first chemical probes and leads for developing the
first clinical candidates targeting the alternative lengthening of telomeres (ALT) pathway. Cellular immortality is
essential for tumorigenesis and is achieved by the action of telomerase in ~85% of cancers and the ALT
mechanism in ~15% of cancers. ALT is poorly understood, but most ALT cells appear to share a common
biomarker, extrachromosomal C-circles, that are predicted to be involved in telomere maintenance. In many
cancers, the ALT phenotype is associated with high grade and poor prognosis. This suggests that targeting the
ALT pathway will have significant impact in a substantial number of disease states. In addition to the clinical
relevance of ALT, at a fundamental level, the mechanisms of ALT are not well understood. To address these
unmet needs, we will identify chemical probes that target ALT using C-circles as a readout for the ALT
phenotype. The power of our approach is that the readout is phenotype specific and the compound libraries
we will use include target specific libraries, with a focus on epigenetic and kinase targets, as well as diverse
chemical libraries. The target focused libraries will allow a chemical genetics approach towards unraveling ALT
mechanisms. We anticipate the discovery of small, drug-like molecules to serve as starting points for the
discovery of ALT-cancer cell selective agents and probes. We predict that screening target-focused libraries
for an ALT-specific phenotype will allow efficient production of chemical probes that will be transformative in
unraveling the mechanisms of ALT and allow the evaluation ALT-specific anticancer approaches.

## Key facts

- **NIH application ID:** 10046962
- **Project number:** 1R03CA252796-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** MICHAEL B JARSTFER
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $155,500
- **Award type:** 1
- **Project period:** 2020-07-02 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10046962

## Citation

> US National Institutes of Health, RePORTER application 10046962, Targeting ALT-Cancer (1R03CA252796-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10046962. Licensed CC0.

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