Abstract
The understanding of the barriers to effective treatment of cancer is rapidly expanding. As the molecular pathways of apoptosis become better understood, the mechanisms by which cancer cells evade the apoptotic effect of standard chemotherapeutic agents are revealed. Protein kinase B/AKT mediates a potent survival/anti-apoptotic signal when activated; many cancers have been observed to harbor constitutive activation. The mechanism of constitutive activation of AKT in cancer is not usually due to mutation or amplification of the gene, but through activation of upstream signaling events. Extensive preliminary data has shown that inhibition of AKT restores apoptotic sensitivity in various cancers to diverse chemotherapeutic agents, yet the optimal mechanism of inhibition of AKT has yet to be clearly defined. Pancreatic cancer is one of the most difficult to treat given its extreme resistance to the cytotoxic effect of traditional therapy; investigations into therapies to restore apoptotic sensitivity have identified AKT as a potenial target for inhibition. The evolving targeted inhibition of AKT, whether directly or indirectly, is an active area of research with tremendous potential in cancer therapy, and pancreatic cancer specifically, and this field of research is discussed in the current review.
Keywords: Akt, pancreatic cancer, NF-κB, autophagy, apoptosis
Current Cancer Therapy Reviews
Title: Targeted Inhibition of AKT in Pancreatic Cancer
Volume: 5 Issue: 4
Author(s): Tawnya L. Bowles, Colin Parsons, Diego J. Muilenburg and Richard J. Bold
Affiliation:
Keywords: Akt, pancreatic cancer, NF-κB, autophagy, apoptosis
Abstract: The understanding of the barriers to effective treatment of cancer is rapidly expanding. As the molecular pathways of apoptosis become better understood, the mechanisms by which cancer cells evade the apoptotic effect of standard chemotherapeutic agents are revealed. Protein kinase B/AKT mediates a potent survival/anti-apoptotic signal when activated; many cancers have been observed to harbor constitutive activation. The mechanism of constitutive activation of AKT in cancer is not usually due to mutation or amplification of the gene, but through activation of upstream signaling events. Extensive preliminary data has shown that inhibition of AKT restores apoptotic sensitivity in various cancers to diverse chemotherapeutic agents, yet the optimal mechanism of inhibition of AKT has yet to be clearly defined. Pancreatic cancer is one of the most difficult to treat given its extreme resistance to the cytotoxic effect of traditional therapy; investigations into therapies to restore apoptotic sensitivity have identified AKT as a potenial target for inhibition. The evolving targeted inhibition of AKT, whether directly or indirectly, is an active area of research with tremendous potential in cancer therapy, and pancreatic cancer specifically, and this field of research is discussed in the current review.
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Bowles L. Tawnya, Parsons Colin, Muilenburg J. Diego and Bold J. Richard, Targeted Inhibition of AKT in Pancreatic Cancer, Current Cancer Therapy Reviews 2009; 5 (4) . https://dx.doi.org/10.2174/157339409789712654
DOI https://dx.doi.org/10.2174/157339409789712654 |
Print ISSN 1573-3947 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6301 |
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Current progress in Protein Degradation and Cancer Therapy
argeted Protein Degradation is gaining momentum in cancer therapy, it facilitate targeting undruggable proteins, it overcome cancer resistance and avoid undesirable side effects. Thus small molecules degraders have emerged as novel therapeutic strategy. Targeted protein degradation (TPD), the process of eliminating a protein of interest hold a great promise for ...read more
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