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Treatment of Malignant Neoplasms
University of Basel
Gene therapy
Oncology
Hit To Lead or Lead Optimization
• MDM2 as a therapeutic target in the substantial cohort of ER-positive, GATA3-mutant breast cancer patients. With MDM2 inhibitors widely available, our findings can be rapidly translated into clinical trials to evaluate in-patient efficacy.
• Capitalizing on a newly identified synthetic lethal interaction between GATA3 and MDM2, this invention provides for an innovative new approach to pharmacologically inhibit MDM2 with the ultimate goal of targeting GATA3 deficiency in cancer treatment.
• Inhibition of MDM2 hampers cell proliferation and induces apoptosis in cells with reduced GATA3 activity. Since GATA3 deficiency has been identified in breast, bladder or prostate cancer, the technology offers the potential to develop treatments for various neoplasms, in particular malignant neoplasms.
• The invention includes the use of a number of MDM2 inhibitors, and correlates GATA3 status as a predictive biomarker of response. The approach has been confirmed in vitro and in animal models.
WO2021228814A1
GATA3 and MDM2 are synthetic lethal in estrogen receptor-positive breast cancers. Communications Biology, (2022)
