Drugging the guardian of the genome for personalized cancer therapy

Our approach

We combine our 20 years of experience working with the p53 tumor suppressor protein with the cutting-edge methodologies to establish a bespoke treatment for patients with mutations in the TP53 gene.

Our work on PubMed

Our science in three milestones

First

Discovery of the mechanism of APR-246/MQ (eprenetapopt)-induced thermostabilization and rescue of the missense mutant p53 proteins.

Second

Discovery of a novel allosteric mechanism of dual inhibition of p53/MDM2 and p53/MDM4 interactions in cancer cells.

Third

Novel way to restore the TAp73 tumor suppressor for improved therapy in cancers with TP53 gene mutations.

About us

Our goal is to identify effective, specific, and selective treatments for solid and hematological cancers that can be rapidly translated into clinical practice. Towards that goal, we use generic mutant p53 rescue compounds and repurposed drugs to reactivate p53 proteins in cell lines and unique pre-clinical cancer models, including primary cells and humanized mouse models. We also strive to understand how p53 affects longevity by performing comparative proteins' sequence analysis in short-and long-lived species to understand which critical nodes in the p53 pathway are responsible for longevity in the Animal Kingdom. We hope that, in the future, this knowledge could be translated to modulate physiological aging in humans.

Department of Oncology-Pathology, Karolinska Institute and Karolinska University Hospital

News

Our new preprint on the allosteric regulation of the p53 tumor suppressor and the challenges of current AI algorithms in resolving the structure of IDPs is online and available here.

'Killing by proximity' - a quick, new preprint from the Lab highlighting the latest reports on exploiting mutant p53 as a molecular glue to kill cancer cells harbouring p53-Y220C missense variant and the background hint on TAPTAC with p53 staple peptide. Read here