Andrus Gerontology Center, Dept of Biological Sciences and Norris Cancer Center, University of Southern California, 3715 McClintock Avenue, Los Angeles, CA 90089-0191, United States.
Drug Resist Updat. 2012 Feb-Apr;15(1-2):114-22. doi: 10.1016/j.drup.2012.01.004. Epub 2012 Mar 4.
The selection of chemotherapy drugs is based on the cytotoxicity to specific tumor cell types and the relatively low toxicity to normal cells and tissues. However, the toxicity to normal cells poses a major clinical challenge, particularly when malignant cells have acquired resistance to chemotherapy. This drug resistance of cancer cells results from multiple factors including individual variation, genetic heterogeneity within a tumor, and cellular evolution. Much progress in the understanding of tumor cell resistance has been made in the past 35 years, owing to milestone discoveries such as the identification and characterization of ABC transporters. Nonetheless, the complexity of the genetic and epigenetic rewiring of cancer cells makes drug resistance an equally complex phenomenon that is difficult to overcome. In this review, we discuss how the remarkable changes in the levels of glucose, IGF-I, IGFBP-1 and in other proteins caused by fasting have the potential to improve the efficacy of chemotherapy against tumors by protecting normal cells and tissues and possibly by diminishing multidrug resistance in malignant cells.
化疗药物的选择基于对特定肿瘤细胞类型的细胞毒性和对正常细胞和组织的相对低毒性。然而，正常细胞的毒性带来了主要的临床挑战，特别是当恶性细胞已经对化疗产生耐药性时。癌细胞的这种耐药性是由多种因素引起的，包括个体差异、肿瘤内的遗传异质性和细胞进化。由于 ABC 转运蛋白的鉴定和特征描述等里程碑式的发现，过去 35 年来，人们对肿瘤细胞耐药性的理解取得了很大进展。尽管如此，癌细胞的遗传和表观遗传重排的复杂性使得耐药性成为一种同样复杂的现象，难以克服。在这篇综述中，我们讨论了禁食引起的葡萄糖、IGF-I、IGFBP-1 及其他蛋白质水平的显著变化如何通过保护正常细胞和组织，并可能通过减少恶性细胞的多药耐药性，有可能提高化疗对肿瘤的疗效。
