Project Details
Projekt
Metmorfin as adjuvant therapy for glioblastoma - a pathway to clinical phase I/II-trials
Applicants
Professor Dr. Michael Leitzmann; Dr. Corinna Seliger
Subject Area
Hematology, Oncology
Term
from 2014 to 2017
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 190230491
Glioblastoma is the most malignant primary brain tumor with a mean incidence of 7 cases per 100,000 inhabitants per year. Metformin is the most widely prescribed oral antidiabetic drug. In addition to its hypoglycaemic effects, metformin may also reduce the risk of cancer in diabetic patients (1) . The association between metformin and the risk of glioblastoma has not yet been evaluated. However, recent experimental data suggest meaningful effects of metformin on glioma cells in vitro and in vivo (2-4).We have published studies on glioma epidemiology and metabolism (5, 6). Further, we recently gained access to the Clinical Practice Research Datalink (CPRD) database that includes over 8 million patients in the U.K., preliminarily investigated the effects of metformin on human brain tumor initiating cells (BTIC; unpublished) and developed an in vitro drug testing algorithm thatpredicts treatment response of BTIC (Moeckel et al., submitted).This project will prepare a prospective, randomized Phase II-trial investigating the effect of adjuvant treatment with metformin in patients with glioblastoma. Objective 1 of the project will substantiate the influence of metformin on the incidence and prognosis of glioblastoma. Objective 2 will investigate molecular, cellular and metabolic effects of metformin alone and in combination with temozolomide or inhibitors of MCT-1 in BTIC. Further, we will investigate if response to metformin can be predicted from pre-treated BTIC.Both a detailed molecular and metabolic understanding of responses to metformin as well as a prediction of responders will be pivotal for planning a clinical phase II trial in humans considering the distinct responses of patients that are notorious for clinical trials in patients with GBM. In addition, our epidemiologic subproject allows an observational analysis of the associations between metformin and glioblastoma in an unselected patient cohort adjusted for multiple confounding variables.
DFG Programme
Clinical Research Units
