The field of personalised medicine to provide understanding of the molecular basis of disease and the mechanism of action of chemotherapeutic drugs is constantly growing. A recent study carried out by Schneider et al has highlighted several interesting facts.
This study identifies that:
SAMHD1 is a potential cellular biomarker in the stratification of patients for cytarabine based therapy
SAMHD1 reduces the cytotoxicity of Ara-C in AML
SAMHD1 could be considered as a therapeutic target in AML treatment
High SAMHD1 protein expression correlated with a poor response to cytarabine treatment and a significantly worse overall survival compared to AML patients with low expression levels at diagnosis.
SAMHD1 is a dNTP triphospho-hydrolase which was shown to interfere with the antileukemic activity of cytarabine (Ara-C). dGTP-activated SAMHD1 hydrolysed the active cytarabine metabolite Ara-CTP, which resulted in a drastic reduction of Ara-CTP in the leukemic cells.
This key paper highlighted the importance of biomarkers for the prediction of the therapeutic response to chemotherapeutic drugs, in this case SAMHD1 as a potential cellular biomarker for the stratification of patients with AML who might best respond to Ara-C based therapy. Furthermore, it uncovered a patient- and drug-specific interference mechanism that can be exploited as a drug target in the development of a more tailored treatment approach.
At Epistem we can offer several orthotopic imaging animal models of AML where cytarabine is validated as standard of care. We have extensive experience in in vivo imaging which allows for monitoring of treatment effects in the same animal over time and to detect treatment potentiation and disease regression after introduction of additional therapeutics.
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Schneider et al. SAMHD1 is a biomarker for cytarabine response and a therapeutic target in acute myeloid leukaemia. Nat Med. 2016 Dec 19. doi: 10.1038/nm.4255. [Epub ahead of print]