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KMID : 0606920110190040371
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Biomolecules & Therapeutics
2011 Volume.19 No. 4 p.371 ~ p.389
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Future Cancer Therapy with Molecularly Targeted Therapeutics: Challenges and Strategies
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Kim Mi-Sook
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Abstract
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A new strategy for cancer therapy has emerged during the past decade based on molecular targets that are less likely to be es-sential in all cells in the body, therefore confer a wider therapeutic window than traditional cytotoxic drugs which mechanism of action is to inhibit essential cellular functions. Exceptional heterogeneity and adaptability of cancer impose signifi cant challenges in oncology drug discovery, and the concept of complex tumor biology has led the framework of developing many anticancer thera-peutics. Protein kinases are the most pursued targets in oncology drug discovery. To date, 12 small molecule kinase inhibitors have been approved by US Food and Drug Administration, and many more are in clinical development. With demonstrated clinical effi cacy of bortezomib, ubiquitin proteasome and ubiquitin-like protein conjugation systems are also emerging as new therapeutic targets in cancer therapy. In this review, strategies of targeted cancer therapies with inhibitors of kinases and proteasome systems are discussed. Combinational cancer therapy to overcome drug resistance and to achieve greater treatment benefi t through the additive or synergistic effects of each individual agent is also discussed. Finally, the opportunities in the future cancer therapy with molecularly targeted anticancer therapeutics are addressed.
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KEYWORD
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Targeted cancer therapy, Small molecule kinase inhibitor, Ubiquitin proteasome system (UPS) inhibitor, Ubiquitin-like protein (UBL) conjugation system inhibitor, Combination of molecularly targeted cancer therapy, Personalized medicine
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