Molekylär karakterisering och farmakologisk reglering av Topoisomeras för minskad biverkan vid cancerbehandling

Diarienummer 2016-02055
Koordinator Karolinska Institutet - CMB
Bidrag från Vinnova 1 920 000 kronor
Projektets löptid augusti 2016 - juni 2019
Status Pågående
Ansökningsomgång VINNMER Marie Curie Incoming 2016-03-16

Syfte och mål

This research project aims to decipher the mechanism of topoisomerases (TOPs) and how their activity is orchestrated during transcription to target the regulation of TOPs activity with new drug candidates. The specific aims are: Aim 1. To determine the molecular mechanism by which the cancer-related transcription factor MYC regulates TOP1 and TOP2 activities. Aim 2. To determine the molecular mechanism by which the chromatin factor BRD4 regulates TOP1 activity Aim 3. To perform combinatorial drug screens to discover new and more effective TOP inhibitors

Förväntade effekter och resultat

This proposal promises a detailed understanding of TOP biology and the molecular characterization of TOP/MYC and TOP/BRD4 regulatory networks during transcription. The work will also lead to the identification of new drug combinations. Once the targeting strategy has been defined, drug companies could be engaged to advance the findings towards phase I/II clinical trials. The worldwide market for anti-cancer drugs is economically significant. Therefore, this proposal has the potential for rapid clinical development for the benefit of individual patients and of the society.

Planerat upplägg och genomförande

Dr. Baranello will lead this project in the Department of Cell and Molecular Biology (CMB) of Karolinska Institutet. She and her team members will carry out the experiments with guidance and assistance from NIH scientists when needed. By establishing this collaboration, Dr. Baranello and her group, and in the long term CMB and KI, will have access to a world-class anti-cancer research partner equipped with cutting-edge technologies and unique reagents. This transition will connect CMB and NIH scientists and help to assure long term collaboration even after completion of this project.

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