Potential of p38 MAP kinase inhibitors in the treatment of cancer.
The involvement of chronic inflammation in tumor development and progression is reviewed. Based on the natural history of certain diseases and epidemiology studies, a strong association has been established between particular chronic inflammatory conditions and eventual tumor appearance. Solid tumors require a stroma for their growth and recruit macrophages to synthesize essential growth and angiogenic factors that they do not have the capacity to produce. The microenvironment of the local host tissue appears to be an active participant in exchanging cytokines and enzymes with tumor cells that modify the local extracellular matrix, stimulate migration, and promote tumor angiogenesis, proliferation and survival. The role of p38 MAP kinase as a therapeutic target for treating cancer is discussed.
Schultz
Richard M
RM
Lilly Research Laboratories, Division of Cancer Research, Indianapolis, IN 46285, USA. Schultz_Richard_M@Lilly.com
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016207:Cytokines / Q000502:physiology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D016207:Cytokines; D004791:Enzyme Inhibitors; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases