Adèle C. Green

Many cancers have been cured by chemotherapeutic agents. However, other cancers are intrinsically drug resistant, and some acquire resistance following chemotherapy. Cloning of the cDNA for the human MDR1 gene (also known as PGY1), which encodes the multidrug efflux protein P-glycoprotein, has made it possible to measure levels of MDR1 RNA in human cancers. We report the levels of MDR1 RNA in greater than 400 human cancers. MDR1 RNA levels were usually elevated in untreated, intrinsically drug-resistant tumors, including those derived from the colon, kidney, adrenal gland, liver, and pancreas, as well as in carcinoid tumors, chronic myelogenous leukemia in blast crisis, and cell lines of non-small cell carcinoma of the lung (NSCLC) with neuroendocrine properties. MDR1 RNA levels were occasionally elevated in other untreated cancers, including neuroblastoma, acute lymphocytic leukemia (ALL) in adults, acute nonlymphocytic leukemia (ANLL) in adults, and indolent non-Hodgkin's lymphoma. MDR1 RNA levels were also increased in some cancers at relapse after chemotherapy, including ALL, ANLL, breast cancer, neuroblastoma, pheochromocytoma, and nodular, poorly differentiated lymphoma. Many types of drug-sensitive and drug-resistant tumors, including NSCLC and melanoma, contained undetectable or low levels of MDR1 RNA. The consistent association of MDR1 expression with several intrinsically resistant cancers and the increased expression of the MDR1 gene in certain cancers with acquired drug resistance indicate that the MDR1 gene contributes to multidrug resistance in many human cancers. Thus, evaluation of MDR1 gene expression may prove to be a valuable tool in the identification of individuals whose cancers are resistant to specific agents. The information may be useful in designing or altering chemotherapeutic protocols in these patients.

PURPOSE: Regular sunscreen use prevents cutaneous squamous cell carcinoma long term, but the effect on melanoma is highly controversial. We evaluated whether long-term application of sunscreen decreases risk of cutaneous melanoma. PARTICIPANTS AND METHODS: In 1992, 1,621 randomly selected residents of Nambour, a township in Queensland, Australia, age 25 to 75 years, were randomly assigned to daily or discretionary sunscreen application to head and arms in combination with 30 mg beta carotene or placebo supplements until 1996. Participants were observed until 2006 with questionnaires and/or through pathology laboratories and the cancer registry to ascertain primary melanoma occurrence. RESULTS: Ten years after trial cessation, 11 new primary melanomas had been identified in the daily sunscreen group, and 22 had been identified in the discretionary group, which represented a reduction of the observed rate in those randomly assigned to daily sunscreen use (hazard ratio [HR], 0.50; 95% CI, 0.24 to 1.02; P = .051). The reduction in invasive melanomas was substantial (n = 3 in active v 11 in control group; HR, 0.27; 95% CI, 0.08 to 0.97) compared with that for preinvasive melanomas (HR, 0.73; 95% CI, 0.29 to 1.81). CONCLUSION: Melanoma may be preventable by regular sunscreen use in adults.