MK-2206, an Akt inhibitor, enhances carboplatinum/paclitaxel efficacy in gastric cancer cell lines

Almhanna, Khaldoun; Cubitt, Christopher L.; Zhang, Shumin; Kazim, Sabiha; Husain, Kazim; Sullivan, Daniel M.; Sebti, Saı̈d M.; Malafa, Mokenge P.

doi:10.4161/cbt.25939

Cited by 25 publications

(12 citation statements)

References 14 publications

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“…Recently, combined (rather than single‐agent) chemotherapy has been found to be a superior treatment method (Almhanna et al , ). Notably, in our previous study, a combination treatment with low‐doses of ROS inducers produces abundant ROS generation and triggers cell apoptosis (Zou et al , ).…”

Section: Discussionmentioning

confidence: 99%

Curcuminoid EF24 enhances the anti‐tumour activity of Akt inhibitor MK‐2206 through ROS‐mediated endoplasmic reticulum stress and mitochondrial dysfunction in gastric cancer

Chen

Dai

Zou

et al. 2017

British J Pharmacology

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Section: Discussionmentioning

confidence: 99%

Curcuminoid EF24 enhances the anti‐tumour activity of Akt inhibitor MK‐2206 through ROS‐mediated endoplasmic reticulum stress and mitochondrial dysfunction in gastric cancer

Chen

Dai

Zou

et al. 2017

British J Pharmacology

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“…Prior studies have shown anticancer activity of MK-2206 across multiple tumor types as well as synergy with established chemotherapeutic agents in NSCLC (Agarwal et al 2014; Almhanna et al 2013; Hirai et al 2010; Konopleva et al 2014; Rashmi et al 2014). Additional work has indicated synergy and enhanced cytotoxicity when MK-2206 is combined with EGFR inhibitors including erlotinib, gefitinib, and cetuximab in the context of a limited number of NSCLC, breast, and glioma cell lines (Cheng et al 2012; Hirai et al 2010; Iida et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Effects of AKT inhibition on HGF-mediated erlotinib resistance in non-small cell lung cancer cell lines

Holland

Chinn

Lara

et al. 2014

J Cancer Res Clin Oncol

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Purpose Acquired resistance to erlotinib in patients with EGFR-mutant non-small cell lung cancer can result from aberrant activation of alternative receptor tyrosine kinases, such as the HGF-driven c-MET receptor. We sought to determine whether inhibition of AKT signaling could augment erlotinib activity and abrogate HGF-mediated resistance. Methods The effects of MK-2206, a selective AKT inhibitor, were evaluated in combination with erlotinib on a large panel of 13 lung cancer cell lines containing different EGFR or KRAS abnormalities. The activity of the combination was assessed using proliferation assays, flow cytometry and immunoblotting. The MEK inhibitor PD0325901 was used to determine the role of the MAP kinase pathway in erlotinib resistance. Results The combination of MK-2206 and erlotinib resulted in synergistic growth inhibition independent of EGFR mutation status. In cell lines where HGF blocked the anti-proliferative and cytotoxic effects of erlotinib, MK-2206 could restore cell cycle arrest, but MEK inhibition was required for erlotinib-dependent apoptosis. Both AKT and MEK inhibition contributed to cell death independent of erlotinib in the T790M-containing H1975 and the EGFR-WT cell lines tested. Conclusions These findings illustrate the potential advantages and challenges of combined signal transduction inhibition as a generalized strategy to circumvent acquired erlotinib resistance.

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“…Now, research has proved that the AKT inhibitor could reverse the drug resistance of gastric cancer cells. 71 Further validation and application researches have been carried out and would get promising results for clinical works. 72…”

Section: Change Of Apoptosis and Autophagy Dysfunction Of Apoptosis Pmentioning

confidence: 99%

<p>A Review of Research Progress in Multidrug-Resistance Mechanisms in Gastric Cancer</p>

Ruan¹,

Liu²,

Tao³

et al. 2020

OTT

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Gastric cancer is one of the most common malignant tumors, and it is also one of the leading causes of cancer death worldwide. Because of its insidious symptoms and lack of early dictation screening, many cases of gastric cancer are at late stages which make it more complicated to cure. For these advanced-stage gastric cancers, combination therapy of surgery, chemotherapy, radiotherapy and target therapy would bring more benefit to the patients. However, the drug-resistance to the chemotherapy restricts its effect and might lead to treatment failure. In this review article, we discuss the mechanisms which have been found in recent years of drug resistance in gastric cancer. And we also want to find new approaches to counteract chemotherapy resistance and bring more benefits to the patients.

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MK-2206, an Akt inhibitor, enhances carboplatinum/paclitaxel efficacy in gastric cancer cell lines

Cited by 25 publications

References 14 publications

Curcuminoid EF24 enhances the anti‐tumour activity of Akt inhibitor MK‐2206 through ROS‐mediated endoplasmic reticulum stress and mitochondrial dysfunction in gastric cancer

Curcuminoid EF24 enhances the anti‐tumour activity of Akt inhibitor MK‐2206 through ROS‐mediated endoplasmic reticulum stress and mitochondrial dysfunction in gastric cancer

Effects of AKT inhibition on HGF-mediated erlotinib resistance in non-small cell lung cancer cell lines

<p>A Review of Research Progress in Multidrug-Resistance Mechanisms in Gastric Cancer</p>

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