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Studying the transition of liver cirrhosis to liver cancer

  • Researcher: Dr Raul Mendez
  • Institution: Institute for Research in Biomedicine, Barcelona, Spain
  • Award Amount: £170,400 for 3 years from 1st January 2016
  • Cancer Type: Liver Cancer
Studying the transition of liver cirrhosis to liver cancer
Dr Raul Mendez is studying how and why liver damage can lead to cancer.

Hepatocellular carcinoma is the most common type of liver cancer and a leading cause of death worldwide. Most people who develop hepatocarcinoma have underlying cirrhosis (scarring of the liver caused by continuous, long-term liver damage). The management of these patients continues to be a critical clinical problem, for which few therapeutic options are available. In fact, liver cancer is expected to increase in incidence due to the current “obesity epidemic”.

Dr Mendez explains “Current treatments are mostly limited to liver resection (removal of part or all of the liver) and transplants. But these options are severely restricted by tumour size and localization, and by liver availability for transplantation. Therefore, there is still a clear need for new treatment strategies to improve the therapeutic outcome of patients suffering from liver cancer. Understanding more precisely the molecular alterations underlying the transition from cirrhosis to hepatocarcinoma will contribute to this aim.”

He continued “We hypothesize that transition from liver cirrhosis to hepatocarcinoma could be regulated by CPEB proteins. Indeed we have shown that CPEBs shorten a highly specific region of RNAs (a copy of the information contained in the DNA) that holds most signals determining whether an RNA molecule is made into protein or not. Thus, CPEBs “take off the brakes" for RNAs involved in tumor growth. This allows the RNAs to be made into proteins and promotes tumour development.

We have also found that CPEB expression (which switches on the making of new proteins that favours tumour growth and new blood vessel formation) is increased in several human tumours and cirrhotic livers. It plays a major role regulating processes like angiogenesis (the formation of new blood vessels) which is crucial for tumour growth.”

He added “With this funding we aim to determine the role and therapeutic potential of CPEBs in the transition from cirrhosis to hepatocarcinoma. Targeting CPEBs may have a great potential for clinical application in liver cancer.”

He concluded “The support from the Worldwide Cancer Research has allowed us to assemble a multidisciplinary team with an expert in Liver physiology (Mercedes Fernandez, IDIBAPS), a leading Hepato-oncologist (Jordi Bruix, Clinic Hospital) and an expert in Gene expression regulation (Raúl Méndez, IRB). With this broad perspective we will approach the transition from cirrhosis to liver cancer from a new and previously unexplored angle. We aim to translate the molecular mechanism(s) responsible of the tumour initiation to diagnostic, and in the longer-term therapeutic, tools with clinical application. We are very grateful for the confidence deposited by the public in our project and very aware on the responsibility to deliver results that go beyond our respective academic fields into discoveries with social impact.”
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