# Mechanisms of action and therapeutic targeting of the CARM1-NFIB axis in small cell lung cancer

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2024 · $618,833

## Abstract

ABSTRACT
Treatment options for small cell lung cancer (SCLC) patients have remained largely unchanged for 3 decades,
with no new FDA-approved treatments for 20 years, and no targeted therapies. We recently performed a screen
for targets of an arginine methyltransferase called CARM1 and identified the NFI family of transcription factors
as substrates for this PRMT. Importantly, NFIB harbors both oncogenic and metastatic promoting activities in
the context of SCLC development. We confirmed that CARM1 functions as a transcriptional coactivator for NFIB.
Based on these finding, we hypothesize that CARM1 methylation of NFIB is critical for its tumor-promoting
functions. To further support this premise, we have generated a Nfib knockin mouse that harbors a R-to-K
mutation in the CARM1 methylation site. When this mouse is crossed onto a SCLC genetically engineered mouse
model (GEMM) the life expectancy of these mice is lengthened by a third (from 200 to 300 days), which is almost
identical to the impact of Carm1-loss in the same GEMM. These finding raise the possibility of targeting SCLC
with CARM1 small molecule inhibitors. We have also identified an effector molecule (TRIM29) for the CARM1
methylation site on NFIB. In this proposal we plan to: (1) perform a deep mechanistic analysis of this newly
discovered CARM1/NFIB/TRIM29 signaling axis, and (2) investigate the therapeutic potential of targeting this
axis using a battery of pre-clinical mouse models.

## Key facts

- **NIH application ID:** 10879050
- **Project number:** 5R01CA272843-02
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** MARK T. BEDFORD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $618,833
- **Award type:** 5
- **Project period:** 2023-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10879050

## Citation

> US National Institutes of Health, RePORTER application 10879050, Mechanisms of action and therapeutic targeting of the CARM1-NFIB axis in small cell lung cancer (5R01CA272843-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10879050. Licensed CC0.

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