# Bcl-2 as a target in cancer

> **NIH NIH R21** · OREGON STATE UNIVERSITY · 2022 · $204,106

## Abstract

Project Summary
Bcl-2, an anti-cell death protein, is overexpressed in about 40% of all human cancers and contributes to the
development and progression of cancer. Overexpression of Bcl-2 correlates with poor survival and
progression of the disease and correlates with resistance of breast cancer cells to chemotherapeutic drugs
and gamma irradiation. We have discovered a novel pathway to convert Bcl-2 from a cytoprotective to
cytodestructive protein. This dramatic change in Bcl-2 function is brought about by orphan nuclear receptor
Nur77 (which migrates from the nucleus to mitochondria upon stimulation by certain agents) binding, which
exposes a hidden "killer BH3 domain" of Bcl-2. During the course of identifying the minimal functional
domain of Nur77, a nine amino acid peptide that mimics the mechanistic and functional activities of Nur77
was identified. This peptide is able to induce cancer cell death by selectively binding Bcl-2 and converting
Bcl-2 from a protector to a killer protein by inducing conformational changes. The apoptotic effects of Nur77
peptides are not inhibited, but rather potentiated, by Bcl-2 overexpression. Nur77-derived peptides thus
represent a new class of anti-breast cancer agents. We have identified compounds that selectively induced
enhanced death in Bcl-2 overexpressing triple negative breast cancer cells. We now propose to evaluate
the efficacy of the identified lead ‘Bcl-2 functional converters’ on breast cancer stem cells.

## Key facts

- **NIH application ID:** 10321294
- **Project number:** 5R21CA249627-02
- **Recipient organization:** OREGON STATE UNIVERSITY
- **Principal Investigator:** Siva Kumar Kolluri
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $204,106
- **Award type:** 5
- **Project period:** 2021-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10321294

## Citation

> US National Institutes of Health, RePORTER application 10321294, Bcl-2 as a target in cancer (5R21CA249627-02). Retrieved via AI Analytics 2026-08-18 from https://api.ai-analytics.org/grant/nih/10321294. Licensed CC0.

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