Development of predictive biomarker(s) to MTH1 inhibitors

Important results from the project

The overall purpose of this project has been to identify predictive biomarkers for a novel anticancer treatment, MTH1 inhibitor, to improve success rate during clinical trials with the ultimate goal to develop a safe and effective novel anticancer treatment with companion biomarker for cancer patients. We have identified potential biomarkers in preclinical models, developed methods to analyze the biomarker and initiated the confirmation in clinical samples from on-going clinical phase 1 trial.

Expected long term effects

Here we have validated 8-oxodG as a biomarker in preclinical models and initiated the confirmation in clinical samples from the on-going phase 1 clinical trial MASTIFF. Broad cell screens and genetic analysis have identified that hematological cancers are the most sensitive cancers for MTH1i and that the overall mutational and oxidative stress levels are important for response, rather than one specific oncogene. These findings will be used to design the phase 1/2 clinical trial in AML patients.

Approach and implementation

This is a collaborative project between basic researchers, clinicians and business development. Cancer cell lines, disease models, and primary AML patient biopsies have been treated with MTH1i and responses correlated to genetic findings. Methods have been developed and validated in clinical material. Project meetings where results, plans and decisions have been shared and taken have been held regularly. The project has developed according to plan with minor deviations from the original plan.