# Preventing UV-induced immunosuppression and skin carcinogenesis with R-carvedilol

> **NIH NIH R01** · WESTERN UNIVERSITY OF HEALTH SCIENCES · 2023 · $316,087

## Abstract

Skin cancer, particularly non-melanoma skin cancer, is by far the most common malignancy in the US.
Overexposure to ultraviolet (UV) radiation is a main factor causing skin cancer, via inducing DNA damage,
inflammation, and immunosuppression. The β-adrenergic receptor (β-AR) antagonist (β-blocker) carvedilol, a
commonly used drug for cardiovascular disorders, has shown promising activity in preventing UV-induced skin
cancer in vitro and in vivo. However, as a highly potent β-blocker, systemic absorbtion of carvedilol may cause
unwanted cardiovascular effects such as bradycardia and hypotention. To overcome this obstacle, two strategies
are applied: (1) development of a skin targeting nanodelivery system, and (2) examination of the effects of the
non-β-blocking R-carvedilol enantiomer, because carvedilol is a racemic mixture consisting of the β-blocking S-
carvedilol and non-β-blocking R-carvedilol in 1:1 ratio. Preliminary data indicate that topical delivery of
carvedilol loaded nano-transfersome was able to effectively prevent skin cancer without systemic absorption.
Additional data indicate that β-blockade is dispensable for carvedilol's cancer preventive activity. Further
preliminary studies indicate that R-carvedilol, although not a β-blocker, is effective in preventing UV-induced
immunosuppression and skin carcinogenesis without affecting blood pressure. Importantly, both R- and S-
carvedilol inhibit ryanodine receptors (RyRs) by reducing the opening time of this intracellular calcium channel,
and further preliminary data suggest that reducing RyR opening activity represents a previously unexplored
mechanism for skin cancer prevention. Thus, the overall objective of this application is to determine the
molecular target for carvedilol-mediated chemoprevention and examine a novel nanodelivery system of R-
carvedilol as an effective and safe approach for skin cancer prevention. Aim 1 is to test the hypothesis that
carvedilol prevents cancer independently of β-blockade. Aim 2 is to test the hypothesis that reducing RyR activity
mediates carvedilol's cancer preventative activity. Aim 3 is test the hypothesis that R-carvedilol can be
formulated in nano-transfersome gel which can be safely and repeatedly applied to the skin without significant
systemic absorption. Since carvedilol is an FDA-approved agent, we anticipate the outcomes from this project
will be readily translated into a cancer preventive regimen for healthy human subjects or individuals with
weakened immune system. Importantly, R-carvedilol, lacking β-blocking activity, is expected to prevent cancer
without cardiovascular disturbance, and therefore should be an excellent drug for skin cancer chemoprevention.

## Key facts

- **NIH application ID:** 10653137
- **Project number:** 5R01CA269653-02
- **Recipient organization:** WESTERN UNIVERSITY OF HEALTH SCIENCES
- **Principal Investigator:** Ying Huang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $316,087
- **Award type:** 5
- **Project period:** 2022-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10653137

## Citation

> US National Institutes of Health, RePORTER application 10653137, Preventing UV-induced immunosuppression and skin carcinogenesis with R-carvedilol (5R01CA269653-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10653137. Licensed CC0.

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