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

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

Similar articles

• Targeting the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway: an emerging treatment strategy for squamous cell lung carcinoma.
  Beck JT, Ismail A, Tolomeo C. Beck JT, et al. Cancer Treat Rev. 2014 Sep;40(8):980-9. doi: 10.1016/j.ctrv.2014.06.006. Epub 2014 Jul 3. Cancer Treat Rev. 2014. PMID: 25037117 Review.
• Structure and ligand-based design of mTOR and PI3-kinase inhibitors leading to the clinical candidates VS-5584 (SB2343) and SB2602.
  Poulsen A, Nagaraj H, Lee A, Blanchard S, Soh CK, Chen D, Wang H, Hart S, Goh KC, Dymock B, Williams M. Poulsen A, et al. J Chem Inf Model. 2014 Nov 24;54(11):3238-50. doi: 10.1021/ci500493m. Epub 2014 Oct 23. J Chem Inf Model. 2014. PMID: 25317974
• Defining biomarkers to predict sensitivity to PI3K/Akt/mTOR pathway inhibitors in breast cancer.
  Gonzalez-Angulo AM, Blumenschein GR Jr. Gonzalez-Angulo AM, et al. Cancer Treat Rev. 2013 Jun;39(4):313-20. doi: 10.1016/j.ctrv.2012.11.002. Epub 2012 Dec 6. Cancer Treat Rev. 2013. PMID: 23218708 Free PMC article.
• PI3K/AKT/mTOR inhibitors in patients with breast and gynecologic malignancies harboring PIK3CA mutations.
  Janku F, Wheler JJ, Westin SN, Moulder SL, Naing A, Tsimberidou AM, Fu S, Falchook GS, Hong DS, Garrido-Laguna I, Luthra R, Lee JJ, Lu KH, Kurzrock R. Janku F, et al. J Clin Oncol. 2012 Mar 10;30(8):777-82. doi: 10.1200/JCO.2011.36.1196. Epub 2012 Jan 23. J Clin Oncol. 2012. PMID: 22271473 Free PMC article.
• Overcoming acquired resistance to anticancer therapy: focus on the PI3K/AKT/mTOR pathway.
  Burris HA 3rd. Burris HA 3rd. Cancer Chemother Pharmacol. 2013 Apr;71(4):829-42. doi: 10.1007/s00280-012-2043-3. Epub 2013 Feb 3. Cancer Chemother Pharmacol. 2013. PMID: 23377372 Review.

Cited by

• Targeting the PI3K/AKT/mTOR pathway: potential for lung cancer treatment.
  Cheng H, Shcherba M, Pendurti G, Liang Y, Piperdi B, Perez-Soler R. Cheng H, et al. Lung Cancer Manag. 2014 Jan 1;3(1):67-75. doi: 10.2217/lmt.13.72. Lung Cancer Manag. 2014. PMID: 25342981 Free PMC article.
• Pharmacological modulation of anti-tumor immunity induced by oncolytic viruses.
  Forbes NE, Krishnan R, Diallo JS. Forbes NE, et al. Front Oncol. 2014 Jul 23;4:191. doi: 10.3389/fonc.2014.00191. eCollection 2014. Front Oncol. 2014. PMID: 25101247 Free PMC article. Review.
• Familial CCM Genes Might Not Be Main Drivers for Pathogenesis of Sporadic CCMs-Genetic Similarity between Cancers and Vascular Malformations.
  Zhang J, Croft J, Le A. Zhang J, et al. J Pers Med. 2023 Apr 17;13(4):673. doi: 10.3390/jpm13040673. J Pers Med. 2023. PMID: 37109059 Free PMC article. Review.
• A Novel Workflow to Enrich and Isolate Patient-Matched EpCAMhigh and EpCAMlow/negative CTCs Enables the Comparative Characterization of the PIK3CA Status in Metastatic Breast Cancer.
  Lampignano R, Yang L, Neumann MHD, Franken A, Fehm T, Niederacher D, Neubauer H. Lampignano R, et al. Int J Mol Sci. 2017 Aug 31;18(9):1885. doi: 10.3390/ijms18091885. Int J Mol Sci. 2017. PMID: 28858218 Free PMC article. Clinical Trial.
• PI3k inhibitors (BKM120 and BYL719) as radiosensitizers for head and neck squamous cell carcinoma during radiotherapy.
  Chuang FC, Wang CC, Chen JH, Hwang TZ, Yeh SA, Su YC. Chuang FC, et al. PLoS One. 2021 Jan 20;16(1):e0245715. doi: 10.1371/journal.pone.0245715. eCollection 2021. PLoS One. 2021. PMID: 33471836 Free PMC article.

References

1. 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
2. 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
3. 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
4. 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].
5. 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

• Full Text Sources

  • Europe PubMed Central
  • Frontiers Media SA
  • PubMed Central

• Other Literature Sources

  • scite Smart Citations

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • NCI CPTAC Assay Portal