# Chemoprevention of environmental UVB-induced skin cancer in immunosuppressed mice

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $330,750

## Abstract

Non-melanoma skin cancers (NMSCs), which include both basal cell (BCCs) and squamous cell carcinomas
(SCCs), are the most common skin neoplasm. Environmental ultraviolet B (UVB) exposure is the main etiologic
factor for these skin cancers. However, other environmental and genetic factors also affect their susceptibility.
In organ transplant recipients (OTRs) the incidence of these cancers increases by 10 to 250 fold. In addition,
these tumors become more aggressive/invasive and metastatic ultimately contributing to augmented morbidity
and mortality in this already morbid population. These cancers in OTRs are not only originated from the
carcinogenic exposure of the transplant recipient but may also be contributed by the donor organ. Circulating
tumor cells have also been found in these patients. At present at least 500,000 OTRs are living in the USA
and their number is growing every year. Skin cancer is the most frequently occurring neoplasm in this
population. Therefore, prevention of skin cancer is desperately required in this population. Oral retinoid showed
some success in this regard however, their administration cause severe toxicity particularly hyperlipidemia.
Here at the University of Alabama at Birmingham, we have developed a relatively non-toxic retinoid without
compromising its efficacy. UAB30, a 9-cis retinoic acid was found to be well-tolerated in humans and in
experimental animals and showed no significant toxicity as compared to placebo group. We, therefore propose
here to test the hypothesis that UAB30 may be highly effective in preventing BCCs and SCCs in chronically
immuno-suppressed mice and acts by inducing DNA damage response (DDR) signaling besides activating
RAR/RXR pathway. For this, we have developed novel genetically engineered Ptch1+/-/SKH-1 mice, which
following chronic UVB irradiation, develop both BCCs and SCCs. We also have compelling preliminary data to
support our hypothesis. Three specific aims are proposed. Specific Aim 1 will investigate the effects of UAB30
on development of BCCs/SCCs in chronically immuno-suppressed UVB-irradiated Ptch1+/-/SKH-1 mice.
Specific Aim 2 will investigate the molecular mechanisms by which UAB30 mediates skin cancer prevention.
In preliminary studies, we found that UAB30 induces DDR signaling. We will therefore assess whether these
responses are identical in immuno-competent and immuno-suppressed animals. Specific Aim 3 will unravel the
molecular basis for the pharmacological action of UAB30 in the experiment settings of normal and immuno-
suppression using in vitro/in vivo approaches. We will study whether alterations fanconi anemia DNA damage
repair pathway are important mechanistic component underlying efficacy of UAB30. In summary, studies
proposed here will not only demonstrate the preclinical efficacy of UAB30 in chronically immuno-suppressed
mice but will also address its molecular mechanism dependent/independent of RAR/RXR.

## Key facts

- **NIH application ID:** 9949377
- **Project number:** 5R01ES026219-05
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Mohammad Athar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $330,750
- **Award type:** 5
- **Project period:** 2016-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9949377

## Citation

> US National Institutes of Health, RePORTER application 9949377, Chemoprevention of environmental UVB-induced skin cancer in immunosuppressed mice (5R01ES026219-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9949377. Licensed CC0.

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