Delineating epigenome regulators as functional survival dependencies in intrahepatic cholangiocarcinoma.

Project Information

EPiCC

Grant agreement ID: 897661

DOI

10.3030/897661

Project closed

EC signature date 26 March 2020

Start date 1 September 2021

End date 31 August 2023

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 207 312,00

EU contribution

€ 207 312,00

Coordinated by

KOBENHAVNS UNIVERSITET
Denmark

Periodic Reporting for period 1 - EPiCC (Delineating epigenome regulators as functional survival dependencies in intrahepatic cholangiocarcinoma.)

Reporting period: 2021-09-01 to 2023-08-31

Summary of the context and overall objectives of the project

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.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

During the EPiCC project, I employed a multifaceted scientific approach to tackle the complexities of iCC. I used advanced genetic editing techniques like CRISPR/Cas9 and high-throughput screening methods to efficiently sift through numerous epigenetic factors and pinpoint those most relevant to iCC. Bioinformatic analyses were instrumental in correlating these findings with patient data, providing a more comprehensive understanding of the disease's genetic underpinnings.
A key result of this project is the identification of the PRKDC gene as essential for a subset of iCC cells, but not for normal liver cells. Known for its role in DNA repair and immune response, PRKDC offers a new avenue for targeted cancer treatments. But this just sets the starting point, as I plan to continue using advanced research methods to delve deeper into how PRKDC operates in iCC. By keeping patient data at the forefront, the goal is to support the development of targeted therapies and potentially improve existing immunotherapies for more effective cancer treatment.
Along the generation of these scientific insights, a range of dissemination activities were undertaken to share our findings. I contributed to scientific publications from the host lab and presented our work at two important international liver cancer conferences, receiving a poster award for the research in one of them. Beyond the scientific community, I engaged with the public through cultural events and educational mentorship of a Danish high school student. Plans are also in place to share our main research paper through social media platforms, further broadening the reach and impact of the EPiCC project.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The EPiCC project has shed some new light on what we currently know about iCC. By identifying PRKDC as a critical epigenetic factor for the survival of a subset of iCC patient-derived cell lines, I have opened up new venues for the development of target treatments, a significant contribution beyond current therapeutic options. As the project progresses, even after the action is finished, we expect to deepen our understanding of the molecular roles of PRKDC in iCC, through continuous application of advanced in vitro and in vivo research methodologies.
The potential implications of this work are far-reaching. Not only could it lead to more effective and personalized treatments for iCC, thereby improving patient outcomes, but it also has the potential to make healthcare more cost-effective by reducing the reliance on less targeted therapies that frequently require higher dosages, and in turn provoke worse secondary effects. From a societal standpoint, enhanced cancer treatment options would mean increased survival rates, better quality of life for patients, and reduced burden on healthcare systems. Overall, the project aims to deliver impacts that are both scientifically groundbreaking and socially beneficial.

Overview of the EPiCC project proposal