Role of Cancer C ell M etabolism in Cancer Therapy and Cancer Prevention
Currently horm one therapy including new horm ones, horm one agonist /an tag o nists, cytokine therapy (including grow th factors (GFs), their receptor inhibitors (GFR-Is), interferons (IFNs), interleukins (ILs), cell differentiation therapy, vita m ins and their sem i-synthetic analogues, gene therapy, antisense therapy, signal transduction pathw ay (STDs), m etabolic suicide genes (or theraputic genes), and m ore recently anti-angiogenesis therapy (angiostatic), telom erases (antitelom - erase therapy), antim etastatic therapy), are the m ost w idely used cancer therapies. These therapeutic cancer strategies are replacing in m any cases conventional can cer therapies (chem otherapy, surgical therapy, and radiation therapy) for m any purposes, and recently becam e the "fourth arm " of cancer treatm ent. Also, herbal m edicine (plant-derived anticancer drugs), and alternative m edicine are briefly m entioned in this chapter. However, their m echanism s of action have not yet been elucidated. A lthough in m any cases they provide dram atic results, in other cases their effects are conflicting. Since there are several interesting reviews regarding the role of these various cancer therapies, however, it would far beyond the scope and length of this chapter to describe them thoroughly, and the reader is therefore directed to them (1-10). This chapter is prim arily focused on the potential role of cancer cell m etabolism and its relevance for cancer treatm ent. Inasm uch as cell m etabolism is a com plex and m ultifaceted phenom enon each of its facets (or aspects) m ay becom e a potential target for cancer neoadjuvant system ic therapy, cancer prevention as w ell as the design and developm ent of novel anticancer drugs (11-12). Since conventional cancer therapy fails to cure approxim ately 50% of cancers it is an im perative goal to develop new therapeutic strategies for can cer treatm ent and also for developm ent of novel anticancer drugs. In the recent years great effort and progress was m ade to understand the m olecular, m etabolic and genetic m echanism s of cancer developm ent and currently is a significant trend to bring the cancer treatm ent and prevention to a m olecular and m etabolic level. M ore recently, isolation and identification of several m etabolic (encoded) active proteins, som e of them are oncoproteins, located in cytosolic, m itochondreal and nuclear m atrix proteins) w hich are the key regulators of a m etabolic gene
expression, a vast netw ork of signaling intracellular pathways (SIP), GF-induced signal transduction (SDS), m etabolic activation and detoxification of cancer drugs, m etabolic therapeutic genes, tyrosine kinase inhibitors (TRK-I), will be increasing ly significant for cancer therapies. T hese studies w ill have a param ou nt significance for the developm ent of novel anticancer drugs that will redefine can cer therapy. Hence, cancer cell m etabolism and its controlling factors will be an exciting field w hich m ay ultim ately provide the greatest pay off for the new cancer therapies (hormone, cytokine, cell differentiation, gene and antisense therapies, antiangiogenises, antitelom erase therapy), as well as for developm ent of novel anticancer drugs. Therefore, a new therapy called "m olecular therapy of cancer" and a new m olecular and m etabolic epidem iology of cancer will em erge and that will profoundly change the nature of cancer treatm ent and chem oprevention.