EPiCC · Delineating epigenome regulators as functional survival dependencies in intrahepatic cholangiocarcinoma.
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2021-09-01 → 2023-08-31
- EU contribution
- €207,312
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Delineating epigenome regulators as functional survival dependencies in intrahepatic cholangiocarcinoma.
The EPiCC project aimed to tackle the urgent issue of intrahepatic cholangiocarcinoma (iCC), a severe liver cancer with few effective treatments and extremely low survival rates. The project had two specific objectives: 1. To identify epigenome regulatory factors that are crucial for the survival of iCC cells using advanced CRISPR/Cas9 genetic editing techniques. 2. To understand the effects of removing these key genes on the cells and the disease as a whole. Using advanced genetic editing techniques, the project identified a crucial gene, PRKDC, that plays a key role in the disease but leaves normal liver cells unaffected. This discovery could pave the way for new, targeted therapies that may extend patient survival and improve quality of life. The project has not only provided new directions for research but also holds promise for developing more effective treatments for this aggressive cancer. Overall, the work offers hope for better understanding and treating a disease that currently has limited therapeutic options.
Data: CORDIS, © European Union
Project objective
Intrahepatic cholangiocarcinoma (iCC) is an aggressive malignancy of the biliary tract with escalating rates among both sexes in EU. Patients survive less than one year from diagnosis due to limited treatments and innate chemoresistance. Genomic analyses have identified recurrent mutations in epigenetic regulators in iCC. Malfunction of such genes has genome-wide consequences for epigenome-remodeling and transcriptome homeostasis, though this remains largely uncharacterized in iCC. Further, the extent to which iCC survival depends on these epigenetic alterations has not been determined. Clarification of these dependencies on epigenetic alterations, which unlike mutations are reversible, is crucial for the development of precision epigenome-targeted therapies for this aggressive disease. Using patient-derived cell lines (PDCLs), I propose to characterize iCC epigenetic survival dependencies to define the functional role(s) of key epigenetic regulators and ensuant epigenome remodeling, in turn identifying putative novel therapeutic targets. To achieve this, I have divided my EPiCC proposal in 2 specific aims:1.Identify iCC-selective functional survival dependencies by state-of-the-art CRISPR/Cas9 screening.2.Characterize the anti-neoplastic cellular and (epi)genomic consequences induced by the top epigenome regulator loss.Through integrating novel comprehensive approaches in iCC (CRISPR/Cas9 screening, R-loop mapping) with robust patient models (primary cells, omics from patient samples), I will provide novel insight into the epigenetic landscape of iCC and identify potential targets for future development of epigenetic-based precision medicine. This study will be supervised by Dr. Andersen, leading expert in the field of hepatobiliary cancers and translational genomics research. Therefore, EPiCC will provide me with new scientific expertise (both technical and transferable skills), a broader network and open new research avenues to follow up in my career.
Original text from CORDIS.
Participants
- KOBENHAVNS UNIVERSITET · KOBENHAVNCoordinatorDenmark
Links
Data: CORDIS, © European Union