Protein profiling identifies mTOR pathway modulation and cytostatic effects of Pim kinase inhibitor, AZD1208, in acute myeloid leukemia

Chen, Lisa S.; Yang, Ji Yeon; Han, Liang; Cortes, Jorge; Gandhi, Varsha

doi:10.3109/10428194.2016.1166489

Cited by 20 publications

(24 citation statements)

References 47 publications

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“…However, the cooperation between CX-6258 and CX-5461 is consistent with the data of Kirschner and colleagues, showing that PIM kinase inhibition synergizes with agents that induce a p53 response in their mouse model of MYC-driven prostate cancer such as docetaxel and radiation therapy, standard therapies for recurrent prostate cancer (31). In addition, PIM kinase inhibition with CX-6258 led to a decrease in rpS6 phosphorylation, consistent with recent reports that PIM kinases can phosphorylate TSC2, relieving its suppression of MTORC1 activity (36,42). This inhibition of PIM kinase activation of MTORC1 activity may, at least in part, explain the increased potency of CX-6258 in tumor cells with high MTORC1 activity (e.g., PTEN-null cells).…”

Section: Discussionsupporting

confidence: 89%

The Dual Inhibition of RNA Pol I Transcription and PIM Kinase as a New Therapeutic Approach to Treat Advanced Prostate Cancer

Rebello

Kusnadi

Cameron

et al. 2016

Clinical Cancer Research

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Section: Discussionsupporting

confidence: 89%

The Dual Inhibition of RNA Pol I Transcription and PIM Kinase as a New Therapeutic Approach to Treat Advanced Prostate Cancer

Rebello

Kusnadi

Cameron

et al. 2016

Clinical Cancer Research

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“…Other authors have reported that the effects of AZD1208 on viability and apoptosis vary by cancer type and cell line. In acute myeloid leukemia, AZD1208 induced apoptosis in vitro in some cell lines, but did not induce apoptosis at all in other cell lines [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Targeting PIM kinase as a therapeutic strategy in human hepatoblastoma

et al. 2018

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Increasing incidence coupled with poor prognosis and treatments that are virtually unchanged over the past 20 years have made the need for the development of novel therapeutics for hepatoblastoma imperative. PIM kinases have been implicated as drivers of tumorigenesis in multiple cancers, including hepatocellular carcinoma. We hypothesized that PIM kinases, specifically PIM3, would play a role in hepatoblastoma tumorigenesis and that PIM kinase inhibition would affect hepatoblastoma in vitro and in vivo. Parameters including cell survival, proliferation, motility, and apoptosis were assessed in human hepatoblastoma cells following PIM3 knockdown with siRNA or treatment with the PIM inhibitor AZD1208. An in vivo model of human hepatoblastoma was utilized to study the effects of PIM inhibition alone and in combination with cisplatin. PIM kinases were found to be present in the human hepatoblastoma cell line, HuH6, and in a human hepatoblastoma patient-derived xenograft, COA67. PIM3 knockdown or inhibition with AZD1208 decreased cell survival, attachment independent growth, and motility. Additionally, inhibition of tumor growth was observed in a hepatoblastoma xenograft model in mice treated with AZD1208. Combination therapy with AZD1208 and cisplatin resulted in a significant increase in animal survival when compared to either treatment alone. The current studies showed that PIM kinase inhibition decreased human hepatoblastoma tumorigenicity both in vitro and in vivo, implying that PIM inhibitors may be useful as a novel therapeutic for children with hepatoblastoma.

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“…PIM kinases expression supports survival of chronic lymphocytic leukemia cells and promotes the CXCR4-mTOR dependent migration [ 44 ]. Similarly, mTOR pathway modulation and AZD1208 cytostatic effects are also identified by protein profiling [ 45 ]. mTOR regulation by PIM kinases and their interrelation in other cancers advocate their magnitude in tumorigenesis.…”

Section: Interrelation Of Pi3k/akt/mtor and Pim Pathways In Other mentioning

confidence: 99%

PIM Kinases and Their Relevance to the PI3K/AKT/mTOR Pathway in the Regulation of Ovarian Cancer

et al. 2018

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Ovarian cancer is a medical term that includes a number of tumors with different molecular biology, phenotypes, tumor progression, etiology, and even different diagnosis. Some specific treatments are required to address this heterogeneity of ovarian cancer, thus molecular characterization may provide an important tool for this purpose. On a molecular level, proviral-integration site for Moloney-murine leukemia virus (PIM) kinases are over expressed in ovarian cancer and play a vital role in the regulation of different proteins responsible for this tumorigenesis. Likewise, the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is also a central regulator of the ovarian cancer. Interestingly, recent research has linked the PIM kinases to the PI3K/AKT/mTOR pathway in several types of cancers, but their connection in ovarian cancer has not been studied yet. Once the exact relationship of PIM kinases with the PI3K/AKT/mTOR pathway is acquired in ovarian cancer, it will hopefully provide effective treatments on a molecular level. This review mainly focuses on the role of PIM kinases in ovarian cancer and their interactions with proteins involved in its progression. In addition, this review suggests a connection between the PIM kinases and the PI3K/AKT/mTOR pathway and their parallel mechanism in the regulation of ovarian cancer.

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Protein profiling identifies mTOR pathway modulation and cytostatic effects of Pim kinase inhibitor, AZD1208, in acute myeloid leukemia

Cited by 20 publications

References 47 publications

The Dual Inhibition of RNA Pol I Transcription and PIM Kinase as a New Therapeutic Approach to Treat Advanced Prostate Cancer

The Dual Inhibition of RNA Pol I Transcription and PIM Kinase as a New Therapeutic Approach to Treat Advanced Prostate Cancer

Targeting PIM kinase as a therapeutic strategy in human hepatoblastoma

PIM Kinases and Their Relevance to the PI3K/AKT/mTOR Pathway in the Regulation of Ovarian Cancer

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