# Novel mechanisms of resistance to antiandrogen therapies

> **NIH VA I01** · VA NORTHERN CALIFORNIA HEALTH CARE SYS · 2021 · —

## Abstract

Enzalutamide was approved for the treatment of metastatic castration resistant prostate cancer (CRPC).
Despite these advances that provide survival gains, there is still no cure for CRPC. Resistance to
enzalutamide occurs frequently and the mechanisms are incompletely understood. Hence, dissecting the
specific adaptive/resistant pathways that are responsible for drug resistance in CRPC and identifying novel
strategies targeting these pathways will dramatically impact the care of men with CRPC. Lin28, a RNA
binding protein, acts as an oncogene inducing cell proliferation and transformation. Lin28 suppresses let-7,
a miRNA involved in suppressing androgen signaling. Our preliminary data suggest that Lin28 promotes
castration resistant prostate cancer progression and is associated with resistance to androgen ablation
treatment. Lin28 is upregulated in prostate cancer and its expression correlates with advanced tumor stage.
Together, these studies underscore the importance of Lin28 in promoting prostate cancer progression and
resistance to enzalutamide, suggesting that targeting Lin28 may provide novel therapeutic opportunities for
prostate cancer. This proposal will determine the roles of Lin28 in resistance to enzalutamide, and explore
the potential of targeting Lin28 to overcome resistance. The specific aims of this proposal are: 1. Examine
the roles of Lin28 in the development of resistance to enzalutamide. 2. Determine molecular mechanisms
underlying Lin28-mediated resistance to enzalutamide. 3. Evaluate targeting Lin28 to overcome resistance
to enzalutamide treatment. The proposed studies will identify and characterize a novel resistance
mechanism involving Lin28 and evaluate targeting Lin28 to overcome resistance to enzalutamide treatment.

## Key facts

- **NIH application ID:** 10266014
- **Project number:** 5I01BX004036-04
- **Recipient organization:** VA NORTHERN CALIFORNIA HEALTH CARE SYS
- **Principal Investigator:** Allen C. Gao
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10266014

## Citation

> US National Institutes of Health, RePORTER application 10266014, Novel mechanisms of resistance to antiandrogen therapies (5I01BX004036-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10266014. Licensed CC0.

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