SAMHD1 is a barrier to antimetabolite-based cancer therapies

Sean G Rudd; Torsten Schaller; Nikolas Herold

doi:10.1080/23723556.2017.1287554

SAMHD1 is a barrier to antimetabolite-based cancer therapies

Mol Cell Oncol. 2017 Feb 3;4(2):e1287554. doi: 10.1080/23723556.2017.1287554. eCollection 2017.

Authors

Sean G Rudd¹, Torsten Schaller², Nikolas Herold³

Affiliations

¹ Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet , Stockholm, Sweden.
² Department of Infectious Diseases, Virology, University Hospital Heidelberg , Heidelberg, Germany.
³ Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; Theme of Children´s and Women´s Health, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.

Abstract

The outcome of acute myelogenous leukemia (AML) therapy depends on the propensity of leukemic blasts to accumulate ara-CTP, the active triphosphate of cytarabine (ara-C). We identified sterile α motif and HD domain-containing protein 1 (SAMHD1) as an ara-CTPase that protects cancer cells from cytarabine-induced toxicity. Therefore, we propose targeting SAMHD1 as a strategy to potentiate cytarabine and possibly other antimetabolite-based therapies.

Keywords: AML; SAMHD1; Vpx; ara-C; cancer; leukemia.