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Pharmacol Ther. 2015 Jul;151:41-9. doi: 10.1016/j.pharmthera.2015.03.001. Epub 2015 Mar 5.

PIM kinase (and Akt) biology and signaling in tumors.

Author information

1
Department of Cellular and Molecular Medicine, Tucson, AZ 85724, United States; University of Arizona Cancer Center, Tucson, AZ 85724, United States. Electronic address: warfelna@email.arizona.edu.
2
Department of Medicine, Tucson, AZ 85724, United States; University of Arizona Cancer Center, Tucson, AZ 85724, United States. Electronic address: Akraft@uacc.arizona.edu.

Abstract

The initiation and progression of human cancer is frequently linked to the uncontrolled activation of survival kinases. Two such pro-survival kinases that are commonly amplified in cancer are PIM and Akt. These oncogenic proteins are serine/threonine kinases that regulate tumorigenesis by phosphorylating substrates that control the cell cycle, cellular metabolism, proliferation, and survival. Growing evidence suggests that cross-talk exists between the PIM and Akt kinases, indicating that they control partially overlapping survival signaling pathways that are critical to the initiation, progression, and metastatic spread of many types of cancer. The PI3K/Akt signaling pathway is activated in many human tumors, and it is well established as a promising anticancer target. Likewise, based on the role of PIM kinases in normal and tumor tissues, it is clear that this family of kinases represents an interesting target for anticancer therapy. Pharmacological inhibition of PIM has the potential to significantly influence the efficacy of standard and targeted therapies. This review focuses on the regulation of PIM kinases, their role in tumorigenesis, and the biological impact of their interaction with the Akt signaling pathway on the efficacy of cancer therapy.

KEYWORDS:

Akt; Cancer; Oncogenes; PIM kinases; Therapeutic resistance

PMID:
25749412
PMCID:
PMC4957637
DOI:
10.1016/j.pharmthera.2015.03.001
[Indexed for MEDLINE]
Free PMC Article

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