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Comment
. 2011 Mar;2(3):109-12.
doi: 10.18632/oncotarget.247.

Exploiting p53 status to enhance effectiveness of chemotherapy by lowering associated toxicity

Linda S Steelman  1 , Alberto M Martelli, Ferdinando Nicoletti, James A McCubrey
Affiliations
Comment

Exploiting p53 status to enhance effectiveness of chemotherapy by lowering associated toxicity

Linda S Steelman et al. Oncotarget. 2011 Mar.
No abstract available

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Figures

Figure 1
Figure 1. Exploiting the p53 Gene Status to Induce Mitotic Catastrophe in p53 Mutant Cells but not in Normal Cells
On the left hand side of the figure labeled A, cells with WT p53 undergo cell cycle arrest upon treatment with Nutlin-3a. However if they are then treated with chemotherapeutic drugs they do not under go mitotic catastrophe. If the chemotherapeutic drug is removed effectively, the normal cells will recover, resume cell cycle progression and grow. On the right hand side of the figure labeled B, in p53 mutant cells, the cells do not undergo cell cycle arrest upon treatment with Nutlin-3a. Then upon treatment with chemotherapeutic drugs, the cycling cells undergo mitotic catastrophe.
Figure 2
Figure 2. Enhancing Effects of Chemotherapy on Induction of Mitotic Catastrophe in p53 Mutant Cells by Drugs Targeting mTORC1 and MDM2 and Suppressing Detrimental Effects of Chemotherapy in p53 WT Cells
Metformin and Rapamycin both suppress mTORC1 but by inhibiting different molecular targets. In the studies by Apontes et al, they have shown that both of these mTORC1 inhibitors can interact with Nutlin-3a to protect p53 WT cells but kill p53 mutant cells. Cancer cells are highly sensitive to drugs which target mTORC1, due to the Warburg effect.
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References

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