Cancer and anticancer therapy-induced modifications on metabolism mediatedby carnitine system

An efficient regulation of fuel metabolism in response to internal and envi ronmental stimuli is a vital task that requires an intact carnitine system. The carnitine system, comprehensive of carnitine, its derivatives, and pro teins involved in its tranformation and transport, is indispensable for glu cose and lipid metabolism in cells. Two major functions have been identifie d for the carnitine system: (1) to facilitate entry of long-chain fatty aci ds into mitochondria for their utilization in energy-generating processes; (2) to facilitate removal from mitochondria of short-chain and medium-chain fatty acids that accumulate as a result of normal and abnormal metabolism. In cancer patients, abnormalities of tumor tissue as well as nontumor tiss ue metabolism have been observed. Such abnormalities are supposed to contri bute to deterioration of clinical status of patients, or might induce cance rogenesis by themselves. The carnitine system appears abnormally expressed both in tumor tissue, in such a way as to greatly reduce fatty acid beta-ox idation, and in nontumor tissue. In this view, the study of the carnitine s ystem represents a tool to understand the molecular basis underlying the me tabolism in normal and cancer cells. Some important anticancer drugs contri bute to dysfunction of the carnitine system in nontumor tissues, which is r eversed by carnitine treatment, without affecting anticancer therapeutic ef ficacy. In conclusion, a more complex approach to mechanisms that underlie tumor growth, which takes into account the altered metabolic pathways in ca ncer disease, could represent a challenge for the future of cancer research . (C) 2000 Wiley-Liss, Inc.