Lecture Series Cancer Research - "TARGETING RAS IN COLORECTAL CANCER"- Prof Christine Sers
20/06/2019 11:00 to 20/06/2019 13:00 (Europe/Luxembourg)
Luxembourg,
Luxembourg
Speaker
Prof Christine Sers is Professor for Tumor Systemsbiology, Charité, Universitätsmedizin Berlin; Institute of Pathology, Germany Group leader of the international research group Molecular Tumor Pathology & Tumor Systems Biology Charité, Universitätsmedizin Berlin; Institute of Pathology, Germany.
Abstract
RAS mutations occur early in colorectal cancer (CRC) development and muta-tions are homogenously distributed throughout tumor samples, rendering RAS an ideal therapeutic target. RAS was discovered more than two decades ago, yet no targeted drug has made it into the clinic until now. Conse-quently, targeting RAS downstream effector proteins and mechanisms has turned into an attractive option for advanced treatment of patients. Histone deacetylase inhibitors (HDACi) are considered as a promising novel thera-peutic approach in the light of their potent tumour-selective effects. Their use for treatment of CRC, however have until now demonstrated limited success as a monotherapy in clinical trials. To shed further light on this, the involve-ment of oncogenic RAS as a key driver of CRC, in determining the responsiveness to HDACi has been explored. Using cell culture models harboring conditional oncogenic NRAS or KRAS we uncovered an oncogenic RAS-dependent resistance mechanism characterized by the induction of a reversible senescence-like growth arrest. This proved to function as a fail-safe method allowing RAS-mutant cells for re-entry into cell cycle following the withdrawal of HDACi. The mecha-nism by which this is proposed to occur is via the phosphorylation of c-MYC, priming it for ubiquitin-mediated prote-osomal degradation. While mutant RAS proteins are expressed in every cell of a tumor sample, a strikingly heterogenous response to HDACi was found in CRC canceroids. These findings may confer important clinical implications, and in addition further aid the development of a rational combinatorial therapeutic strategy using HDACi in solid cancers.
About the Lecture & Workshop series - cancer research
The LIH lecture and workshops series in Cancer Research, supported by the FNR and jointly organized with the University of Luxembourg, are gathering internationally recognised speakers to address topics around Cancer Research during 2019-2020. Please find here the current programme for 2019.
These lectures will be followed by a workshop especially dedicated to early-stage researchers.
Attendance to the lecture and workshop are free of charge. Should you be interested in registering for the workshop, please feel free to do so by sending us an email.