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PIK3CA gene aberrancy and role in targeted therapy of solid malignancies

Cancer Gene Therapy volume 27, pages 634–644 (2020)Cite this article

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Abstract

Phosphoinositide kinases (PIKs) are a group of lipid kinases that are important upstream activators of various signaling pathways that drive oncogenesis. Hyperactivation of the PI3K/AKT/mTOR pathways—either via mutations or genomic amplification—confers key oncogenic activity, essential for the development and progression of several solid tumors. Alterations in the PIK3CA gene are associated with poor prognosis of solid malignancies. Contradictory reports exist in the literature regarding the prognostic value of PIK3CA in aggressive cancers, but most available data highlights an important role of PIK3CA mutation in mediating tumorigenesis via increased signaling of the PI3K/AKT/mTOR survival pathway. Several inhibitors of PI3K/AKT/mTOR pathways have been investigated as potential therapeutic options in solid malignancies. This article reviews the role of PIK3CA mutations and inhibitors of the PI3K/AKT/mTOR pathway in cancer and examines association with the clinico-pathological parameters and prognosis.

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Fig. 1: PIK3CA mutations among cancers with high mutation rates.

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Authors and Affiliations

  1. Department of Internal Medicine, University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA

    Owen Willis, Abdurahman Alloghbi & Lance Dworkin

  2. Department of Internal Medicine, University of Kansas School of Medicine, Wichita, KS, USA

    Khalil Choucair

  3. Division of Hematology and Medical Oncology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA

    Laura Stanbery & John Nemunaitis

  4. Toledo Clinic Cancer Centers, Toledo, OH, USA

    Rex Mowat

  5. Department of Surgery, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA

    F. Charles Brunicardi

  6. ProMedica Health System, Toledo, OH, USA

    John Nemunaitis

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Willis, O., Choucair, K., Alloghbi, A. et al. PIK3CA gene aberrancy and role in targeted therapy of solid malignancies. Cancer Gene Ther 27, 634–644 (2020). https://doi.org/10.1038/s41417-020-0164-0

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