Drugging the cancer kinome: progress and challenges in developing personalized molecular cancer therapeutics.
A major goal of cancer research is to translate our understanding of the causation of malignancy at the level of the genome and biochemical pathways into the development of drugs with improved activity and cancer selectivity. This paper provides a personal perspective of the current status of efforts to achieve this goal, with a particular focus on drugging the cancer kinome. Remarkable progress has been made in this area, but many challenges remain. The value of cancer kinome sequencing is emphasized. Three projects in which the author's laboratory is involved are reviewed in detail. These involve the discovery and development of inhibitors of cyclin-dependent kinases, phosphoinositide 3-kinases, and the Hsp90 molecular chaperone.
Workman
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Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey.
D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000627:therapeutic use; D023281:Genomics; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D000081082:Phosphoinositide-3 Kinase Inhibitors
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D018841:HSP90 Heat-Shock Proteins; D000081082:Phosphoinositide-3 Kinase Inhibitors; D018844:Cyclin-Dependent Kinases