Journal
JOURNAL OF CELLULAR BIOCHEMISTRY
Volume 102, Issue 3, Pages 580-592Publisher
WILEY
DOI: 10.1002/jcb.21500
Keywords
cancer; targeted therapy; cell signaling; drug-discovery; natural products
Categories
Funding
- NCI NIH HHS [CA-16672, P01 CA-91844, P30 CA016672] Funding Source: Medline
- PHS HHS [P50] Funding Source: Medline
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In this age of targeted therapy, the failure of most current drug-discovery efforts to yield safe, effective, and inexpensive drugs has generated widespread concern. Successful drug development has been stymied by a general focus on target selection rather than clinical safety and efficacy. The very process of validating the targets themselves is inefficient and in many cases leads to drugs having poor efficacy and undesirable side effects. Indeed, some rationally designed drugs (e.g., inhibitors of receptor tyrosine kinases, tumor necrosis factor (TNF), cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), bcr-abl, and proteasomes) are ineffective against cancers and other inflammatory conditions and produce serious side effects. Since any given cancer carries mutations in an estimated 300 genes, this raises an important question about how effective these targeted therapies can ever be against cancer. Thus, it has become necessary to rethink drug development strategies. This review analyzes the shortcomings of rationally designed target-specific drugs against cancer cell signaling pathways and evaluates the available options for future drug development.
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