22CE – Topical Chemoprevention of Non-melanoma Skin Cancer

Status: Filled – Yuri Kwon
Intern: Yuri Kwon
Faculty Name: craig-elmets
Primary Faculty Appointment: UAB
UAB/HA Department: Dermatology
Campus Address: VH501
Telephone Number: (205) 276-8652
Email: celmets@uabmc.edu or Click to Send E-Mail
For how many summers have you served as a preceptor: 2
CCC Research Area: Experimental Therapeutics
Number of hours per week that the preceptor will personally supervise or work with the intern: 4
Other faculty, staff, or graduate students who may help to supervise the intern:
1. Craig Elmets, MD and Olufolakemi Awe, MD
2. Leslie Roop
Title of Project: 22CE – Topical Chemoprevention of Non-melanoma Skin Cancer
Project Description:

Non-melanoma skin cancers (NMSCs; cutaneous basal cell carcinomas and squamous cell carcinomas) are
the most common malignancies in humans in the United States. They are the source of considerable
morbidity and are a tremendous cost to the health care system. Current methods for their prevention
have consisted primarily of sun and tanning bed avoidance and the regular use of sunscreens.
Unfortunately, these measures have proven inadequate, and in contrast to most other malignancies,
the incidence of NMSCs continues to increase. Two agents that show promise for the prevention of
non-melanoma skin cancers are non-steroidal anti-inflammatory agents (NSAIDs), which inhibit the
cyclooxygenase enzyme, and difluoromethylornithine (DFMO), a non-competitive inhibitor of the
enzyme ornithine decarboxylase. In other organ systems, these agents have synergistic cancer
chemopreventive activities. Because the skin is readily accessible, it may be possible to apply
topical formulations of these agents for the chemoprevention of skin cancers without encountering
the potential for systemic toxicity. We hypothesize that topical application of the COX inhibitor
diclofenac and/or topical DFMO for 9 months is a safe and effective method of reversing biomarkers
associated with the development of non-melanoma skin cancers in subjects at risk for their
development and will prevent the onset of new actinic keratoses. To test our hypothesis, we plan to
conduct a randomized, double-blind, placebo-controlled trial of 100 subjects with a history of
basal cell and/or squamous cell skin cancer and at least 8 actinic keratoses. Patients will be
randomized to receive: topical DFMO + placebo; placebo + topical diclofenac; topical DFMO + topical
diclofenac; placebo + placebo. We will assess whether topical DFMO + topical diclofenac alters
skin biomarkers focusing on prostaglandin E2, polyamines and ornithine decarboxylase, proliferation
and apoptosis markers (Ki67, PCNA, cyclin D1, caspase 3, tunel assay, Bcl-2, Bax), and molecules
in the Akt/ERK1/2 axis. Studies are planned to determine if treatment with topical DFMO and/or
topical diclofenac is well-tolerated without signs of significant toxicity. We will also assess
whether subjects randomized to topical diclofenac and/or topical DFMO develop over a 9 month period
of time fewer new actinic keratoses than those who are placed on placebo. The ultimate goal of
these studies will be to determine whether topical diclofenac and/or DFMO should be evaluated in a
clinical trial for the preventionof non-melanoma skin cancers.

Project Status: Already up and running
Location of Project: Birmingham, AL (UAB)
Proposed Start Date: May 3, 2021
Proposed End Date: August 27, 2021
Expected work schedule for intern: Not very flexible, intern MUST be at work on certain days of the week and at certain times of the day (as may be necessary to interview patients, attend lab meetings, process samples, etc.) and should contribute full-time effort.
Number of days that the student will be expected to come physically to UAB:
More than 1 day per week (prior to start of the internship, gain appropriate waivers and approvals for the student to be on site)
Category of Project: Clinical (Patient Care) Research
Cancer topic: Skin
Does this project involve human subjects: Yes
Does this project involve animal subjects: No

1. interview patients


2. analyze data


3. Prepare abstracts and manuscripts

Preceptor will provide intern with access to the following: Office or desk space, Computer and printer, Supplies needed to complete project, Equipment needed to complete project
Likelihood that intern will be included as an author on one or more publications related to this summer research project: Very likely
Areas in which the ideal candidates will have experience: Clinical Trials, Interview Skills, Manuscript Preparation for Submission to a Journal, Scientific Writing Skills