Targeting Cancer Cell Death with Small Molecule Agents for Potential Therapeutics
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Time has come to switch from morphological to molecular definitions of cell death subroutines, due to substantial progress in biochemical and genetic exploration. Currently, cell death subroutines are defined by a series of precise, measurable biochemical features; these include apoptosis, autophagic cell death and necroptosis. Accumulating evidence has gradually revealed the core molecular machinery of cell death in carcinogenesis; the intricate relationships between cell death subroutines and cancer, however, still need to be clarified. Cancer drug discovery, in particular, has benefitted significantly from a rapid progress in utilization of several small molecule compounds to target different cell death modularity. Thus, this review provides a comprehensive summary of the interrelationships between the cell death subroutines (e.g., apoptosis and autophagic cell death) and relevant anticancer small molecule compounds (e.g., Oridonin and Rapamycin). Moreover, these interconnections between different cell death subroutines may be integrated into the entire cell death network. This would be regarded as a potential cancer target for more small molecule drug discovery. Taken together, these findings may provide new and emerging clues that fill the gap between cell death subroutines and small molecule drugs for future cancer therapy.
Key wordsApoptosis Autophagy Necroptosis Small molecule compounds Cancer therapy
This work was supported by grants from the Key Projects of the National Science and Technology Pillar Program (No. 2012BAI30B02), National Natural Science Foundation of China (Nos. U1170302, 81402496, 81260628, 81303270 and 81172374).
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