# RSK2 in Estrogen Receptor Positive (ER+) Breast Cancer

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $359,985

## Abstract

Endocrine-based therapies have been very effective at reducing mortality but ~ 25% of patients will progress
and only 30% of those with metastatic disease will respond. Therefore, there is a tremendous need to identify
the mechanisms that drive estrogen receptor alpha positive (ER+) breast cancer and promote invasion. We
found that ERα sequesters activated RSK2, a Ser/Thr protein kinase, into the nucleus to promote neoplastic
transformation and invasive tumor growth. Anti-estrogens disrupted the RSK2/ERα complex, driving RSK2
into the cytoplasm with corresponding reduced tumor growth. We hypothesize that failure to disrupt the
interaction between RSK2 and ERα with endocrine-based therapy leads to metastasis. In support of this
hypothesis the RSK2 gene signature stratifies patients with invasive breast cancer based on positivity for
ERα. The mechanism by which RSK2 promotes ER+ breast cancer progression will be identified and
evaluated in patient-derived xenografts (aim 1). We will test whether RSK2 in complex with a tamoxifen-
resistant ERα mutant drives metastasis using engineered ER+ breast lines (aim 2). RSK inhibitors based on
the parent compound, SL0101, will be generated to identify compounds with improved in vivo efficacy to inhibit
ER+ tumor growth and metastasis (aim 3). Data generated in this proposal will be analyzed using the
appropriate statistics for end point and longitudinal analysis. The successful development of a RSK inhibitor
could dramatically improve outcomes for patients with ER+ metastatic breast cancer.

## Key facts

- **NIH application ID:** 9969065
- **Project number:** 5R01CA213201-03
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Deborah Lannigan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $359,985
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9969065

## Citation

> US National Institutes of Health, RePORTER application 9969065, RSK2 in Estrogen Receptor Positive (ER+) Breast Cancer (5R01CA213201-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9969065. Licensed CC0.

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