Diet, signal transduction and carcinogenesis.
The defects in the regulation of cell growth and differentiation that manifest themselves as cancer result from multiple defective genes and their products, which are involved in the processes of cellular signaling, regulation of gene expression and control of the cell through its replication cycle. Each of these molecular defects represents a new target for development of novel therapeutic agents and prophylactic interventions. Evidence suggests that such therapeutic agents will show great efficacy for cells made cancerous by the single targeted defect. However, poor anticancer efficacy for clinically presenting cancer may occur as a result of the multiple molecular lesions. A combined-agent approach seems likely to be more successful, but this will require diagnosis of each tumor in substantially greater detail, down to the molecular level. When such molecular diagnosis becomes generally feasible, it should be possible to use combinations of highly specific agents at very low doses for therapy and ultimately for prevention of tumor metastasis. Chemoprevention in general may be achieved more easily than therapy with mechanism-based interventions, as certain individual lesions, in theory, may be rate limiting for carcinogenesis but may not be a significant contributor to the neoplastic phenotype by the time the tumor presents in the clinic.
Ashendel
C L
CL
Department of Medicinal Chemistry and Pharmacognosy, Purdue University, West Lafayette, IN 47907.
D002471:Cell Transformation, Neoplastic; D003043:Cocarcinogenesis; D004032:Diet; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000209:etiology* / Q000503:physiopathology* / Q000517:prevention & control; D009857:Oncogenes; D015398:Signal Transduction / Q000502:physiology*