AKT as a therapeutic target in multiple myeloma

Abstract

Introduction: Multiple myeloma remains an incurable malignancy with poor survival. Novel therapeutic approaches capable of improving outcomes in patients with multiple myeloma are urgently required. AKT is a central node in the phosphatidylinositol-3-kinase/AKT/mammalian target of rapamycin signaling pathway with high expression in advanced and resistant multiple myeloma. AKT contributes to multiple oncogenic functions in multiple myeloma which may be exploited therapeutically. Promising preclinical data has lent support for pursuing further development of AKT inhibitors in multiple myeloma. Lead drugs are now entering the clinic.

Areas covered: The rationale for AKT inhibition in multiple myeloma, pharmacological subtypes of AKT inhibitors in development, available results of clinical studies of AKT inhibitors and suitable drug partners for further development in combination with AKT inhibition in multiple myeloma are discussed.

Expert opinion: AKT inhibitors are a welcome addition to the armamentarium against multiple myeloma and promising clinical activity is being reported from ongoing trials in combination with established and/or novel treatment approaches. AKT inhibitors may be set to improve patient outcomes when used in combination with synergistic drug partners.

Keywords::

• afuresertib
• AKT
• AKT inhibitor
• alkylphospholipid
• allosteric inhibitor
• ATP-competitive
• MK-2206
• multiple myeloma
• perifosine
• pleckstrin homology domain
• phosphatidylinositol-3-kinase
• triciribine

Acknowledgment

MOD is a recipient of a Clinician Scientist Award from the Health Research Board (Ireland).

Notes

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