Patients who develop large numbers of
skin cancers suffer increased morbidity and mortality. A high
skin cancer risk can result from inherited disorders such as
xeroderma pigmentosum (abnormal repair of UV-induced DNA damage) or the
nevoid basal cell carcinoma syndrome (tumor suppressor gene abnormality). The efficacy of systemic
retinoid skin cancer chemoprevention was first demonstrated in these disorders. Since the mechanism of
cancer prevention was not thought to involve correction of the underlying defect causing the disorder, individuals at high risk for new
skin cancers from other causes may also benefit from this approach. With the success of
organ transplantation, there is a growing population of transplant recipients living long, active lives who also have sustained chronic UV damage. This population is at high risk for developing aggressive
squamous cell carcinomas. In this population, extensive skin involvement with human papilloma virus induced
warts and
actinic keratoses results in difficulty with diagnosis and monitoring for these dangerous
malignancies. Patients who have received treatment with agents that cause DNA damage, such as X-radiation, may also have a high
skin cancer risk.
Retinoid chemoprevention may also be of benefit in the management of selected patients with these iatrogenic conditions. This evolving therapeutic role has heightened the need for the development of new
retinoids, with more efficacy and less toxicity, for
cancer chemoprevention.