Targeting PI3K in Cancer: Any Good News? - PubMed (original) (raw)

Targeting PI3K in Cancer: Any Good News?

Miriam Martini et al. Front Oncol. 2013.

Abstract

The phosphatidylinositol 3-kinase (PI3K) signaling pathway regulates several cellular processes and it's one of the most frequently deregulated pathway in human tumors. Given its prominent role in cancer, there is great interest in the development of inhibitors able to target several members of PI3K signaling pathway in clinical trials. These drug candidates include PI3K inhibitors, both pan- and isoform-specific inhibitors, AKT, mTOR, and dual PI3K/mTOR inhibitors. As novel compounds progress into clinical trials, it's becoming urgent to identify and select patient population that most likely benefit from PI3K inhibition. In this review we will discuss individual PIK3CA mutations as predictors of sensitivity and resistance to targeted therapies, leading to use of novel PI3K/mTOR/AKT inhibitors to a more "personalized" treatment.

Keywords: PI3K; cancer; class II phosphatidylinositol 3-kinase; genetic determinants; therapeutics.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Schematic representation of PI3K pathway and sites of action of PI3K signaling pathway inhibitors in solid tumors and hematological malignancies.

References

    1. Antonescu C. R. (2011). The GIST paradigm: lessons for other kinase-driven cancers. J. Pathol. 223, 251–26110.1002/path.2798 - DOI - PMC - PubMed
    1. Arcaro A., Khanzada U. K., Vanhaesebroeck B., Tetley T. D., Waterfield M. D., Seckl M. J. (2002). Two distinct phosphoinositide 3-kinases mediate polypeptide growth factor-stimulated PKB activation. EMBO J. 21, 5097–510810.1093/emboj/cdf512 - DOI - PMC - PubMed
    1. Arcaro A., Zvelebil M. J., Wallasch C., Ullrich A., Waterfield M. D., Domin J. (2000). Class II phosphoinositide 3-kinases are downstream targets of activated polypeptide growth factor receptors. Mol. Cell. Biol. 20, 3817–383010.1128/MCB.20.11.3817-3830.2000 - DOI - PMC - PubMed
    1. Arkenau H.-T., Jones S. F., Kurkjian C., Infante J. R., Pant S., Burris H. A., et al. (2012). The PI3K/mTOR inhibitor BEZ235 given twice daily for the treatment of patients (pts) with advanced solid tumors. J. Clin. Oncol. 30, abstr. 3097. [ASCO Annual Meeting Proceedings].
    1. Bendell J. C., Rodon J., Burris H. A., De Jonge M., Verweij J., Birle D., et al. (2012). Phase I, dose-escalation study of BKM120, an oral pan-Class I PI3K inhibitor, in patients with advanced solid tumors. J. Clin. Oncol. 30, 282–29010.1200/JCO.2011.36.1360 - DOI - PubMed

LinkOut - more resources