tailieunhanh - Targeting multidrug resistance in cancer

Finally, research is needed to identify other groups that may benefit from anal screening, including women, and to document the efficacy of anal screening programs in lowering the incidence of anal cancer among those at risk. Widespread screenings of high risk groups may be a cost effective opportu- nity to prevent anal cancer and may well result in lower rates of this disease. Public health leaders should give serious consider- ation to encouraging bi-annual screening for all gay and bisexual men, and annual screen- ing for those gay and bisexual men who are living with HIV | REVIEWS r Targeting multidrug resistance in cancer Gergely Szakacs Jill K. Paterson Joseph A. Ludwig Catherine Booth-Genthe and Michael M. Gottesman Abstract Effective treatment of metastatic cancers usually requires the use of toxic chemotherapy. In most cases multiple drugs are used as resistance to single agents occurs almost universally. For this reason elucidation of mechanisms that confer simultaneous resistance to different drugs with different targets and chemical structures multidrug resistance has been a major goal of cancer biologists during the past 35 years. Here we review the most common of these mechanisms one that relies on drug efflux from cancer cells mediated by ATP-binding cassette ABC transporters. We describe various approaches to combating multidrug-resistant cancer including the development of drugs that engage evade or exploit efflux by ABC transporters. Institute of Enzymology Biological Research Center Hungarian Academy of Sciences Budapest Karolina út 29 H-Ỉ5Ỉ8 Hungary. Laboratory of Cell Biology Center for Cancer Research National Cancer Institute National Institutes of Health 37 Convent Drive Room 2Ỉ08 Bethesda Maryland 20892-4256 USA. Correspondence to . e-mail MGottesman@ doi nrd1984 Anticancer drugs can fail to kill cancer cells for various reasons. Drugs are usually given systemically and are therefore subject to variations in absorption metabolism and delivery to target tissues that can be specific to individual patients. Tumours can be located in parts of the body into which drugs do not easily penetrate or could be protected by local environments due to increased tissue hydrostatic pressure or altered tumour vasculature. By analogy to the study of antibiotic resistance in microorganisms research on drug resistance in cancer has focused on cellular resistance due to either the specific nature and genetic background ofthe cancer cell itself or the genetic changes that follow toxic chemotherapy. Until recently .