Highlights in experimental therapeutics.
The past two decades have seen a dramatic change in cancer treatment paradigms. Anticancer agents are no longer being developed based on empiricism and serendipity, but are now being aimed to inhibit a validated target that is relatively specific for tumours rather than normal cells. The vast majority of cancers arise from multiple genetic lesions; thus, sophisticated drug cocktails, or single drugs acting on multiple downstream targets will be needed for successful cancer therapy. Three emerging concepts that are addressing these therapeutic needs and that are key to blocking steps in tumourigenesis will be highlighted in this review: (a) attacking cancer cell immortality by targeting the telomere/telomerase complex; (b) targeting oncogene activation by inhibiting the molecular chaperone Hsp90; and (c) stabilizing tumour suppressor proteins by modulating the ubiquitin-proteasome system.
Burger
Angelika M
AM
Department of Pharmacology and Experimental Therapeutics, Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA. aburger@som.umaryland.edu
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000378:metabolism; D016615:Telomere / Q000235:genetics / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D061988:Proteasome Inhibitors; D025801:Ubiquitin; D019098:Telomerase; D046988:Proteasome Endopeptidase Complex