DiGiovanna J J
Division of Dermatopharmacology, Department of Dermatology, Brown University School of Medicine and Rhode Island Hospital, Providence, Rhode Island 02903, USA.
Med Pediatr Oncol. 2001 May;36(5):564-7. doi: 10.1002/mpo.1131.
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.
患大量皮肤癌的患者发病率和死亡率会增加。遗传性疾病如着色性干皮病（紫外线诱导的DNA损伤修复异常）或痣样基底细胞癌综合征（肿瘤抑制基因异常）可导致皮肤癌风险升高。全身性维甲酸类药物对皮肤癌的化学预防作用最初是在这些疾病中得到证实的。由于人们认为癌症预防机制并不涉及纠正导致该疾病的潜在缺陷，因此因其他原因面临新发皮肤癌高风险的个体也可能从这种方法中获益。随着器官移植的成功，越来越多的移植受者长期过着积极的生活，但他们也遭受着持续的慢性紫外线损伤。这一人群患侵袭性鳞状细胞癌的风险很高。在这一人群中，人乳头瘤病毒引起的疣和光化性角化病广泛累及皮肤，导致对这些危险恶性肿瘤的诊断和监测困难。接受过如X射线等导致DNA损伤药物治疗的患者，皮肤癌风险也可能很高。维甲酸类药物化学预防对患有这些医源性疾病的特定患者的治疗可能也有益处。这种不断演变的治疗作用增加了对开发新的维甲酸类药物的需求，这类药物在癌症化学预防方面疗效更高、毒性更低。
