TY - JOUR
T1 - Targeting AKT for cancer therapy
AU - Shariati, Maryam
AU - Meric-Bernstam, Funda
N1 - Funding Information:
The work of the authors was supported in part by the Nellie B. Connally Breast Cancer Research Endowment, The Cancer Prevention and Research Institute of Texas RP150535, Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy, MD Anderson Cancer Center Support grant (P30 CA016672). We thank Visual Art at the University of Texas, MD Anderson Cancer Center for generating the illustration in Figure 1.
Publisher Copyright:
© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2019/11/2
Y1 - 2019/11/2
N2 - Introduction: Targeted therapies in cancer aim to inhibit specific molecular targets responsible for enhanced tumor growth. AKT/PKB (protein kinase B) is a serine threonine kinase involved in several critical cellular pathways, including survival, proliferation, invasion, apoptosis, and angiogenesis. Although phosphatidylinositol-3 kinase (PI3K) is the key regulator of AKT activation, numerous stimuli and kinases initiate pro-proliferative AKT signaling which results in the activation of AKT pathway to drive cellular growth and survival. Activating mutations and amplification of components of the AKT pathway are implicated in the pathogenesis of many cancers including breast and ovarian. Given its importance, AKT, it has been validated as a promising therapeutic target. Areas covered: This article summarizes AKT’s biological function and different classes of AKT inhibitors as anticancer agents. We also explore the efficacy of AKT inhibitors as monotherapies and in combination with cytotoxic and other targeted therapies. Expert opinion: The complex mechanism following AKT inhibition requires the addition of other therapies to prevent resistance and improve clinical response. Further studies are necessary to determine additional rational combinations that can enhance efficacy of AKT inhibitors, potentially by targeting compensatory mechanisms, and/or enhancing apoptosis. The identification of biomarkers of response is essential for the development of successful therapeutics.
AB - Introduction: Targeted therapies in cancer aim to inhibit specific molecular targets responsible for enhanced tumor growth. AKT/PKB (protein kinase B) is a serine threonine kinase involved in several critical cellular pathways, including survival, proliferation, invasion, apoptosis, and angiogenesis. Although phosphatidylinositol-3 kinase (PI3K) is the key regulator of AKT activation, numerous stimuli and kinases initiate pro-proliferative AKT signaling which results in the activation of AKT pathway to drive cellular growth and survival. Activating mutations and amplification of components of the AKT pathway are implicated in the pathogenesis of many cancers including breast and ovarian. Given its importance, AKT, it has been validated as a promising therapeutic target. Areas covered: This article summarizes AKT’s biological function and different classes of AKT inhibitors as anticancer agents. We also explore the efficacy of AKT inhibitors as monotherapies and in combination with cytotoxic and other targeted therapies. Expert opinion: The complex mechanism following AKT inhibition requires the addition of other therapies to prevent resistance and improve clinical response. Further studies are necessary to determine additional rational combinations that can enhance efficacy of AKT inhibitors, potentially by targeting compensatory mechanisms, and/or enhancing apoptosis. The identification of biomarkers of response is essential for the development of successful therapeutics.
KW - AKT activation
KW - AKT inhibitors
KW - breast and ovarian cancer
KW - combinational therapy
KW - targeted therapy
KW - tumorigenicity
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U2 - 10.1080/13543784.2019.1676726
DO - 10.1080/13543784.2019.1676726
M3 - Review article
C2 - 31594388
AN - SCOPUS:85074283963
SN - 1354-3784
VL - 28
SP - 977
EP - 988
JO - Expert Opinion on Investigational Drugs
JF - Expert Opinion on Investigational Drugs
IS - 11
ER -