They get that tumor cells of the liver recover the ability to self-destruct

25 07 2011

Studying markers that can predict the response of liver tumor cells to epidermal growth factor receptor inhibitors (EGFR)

The discovery could allow advance towards treatments custom in this type of tumors

Inhibition of epidermal growth factor receptor (EGFR) It slows the growth of liver tumor cells and makes them sensitive to the suppressing action of the cytokine TGF-beta, by activating mechanisms of programmed death (apoptosis). This is the result of an investigation conducted by researchers in the biological key of the invasive Phenotype and metastatic group of the IDIBELL, led by Isabel Fabregat.

The results of the study could lead to the development of new therapies against liver cancer custom. The work is published in the August issue of the Magazine Journal of Hepatology.

Hepatocellular carcinoma is one of the tumors with more mortality in the world and the fifth most common. The appearance of this tumor is related to several molecular alterations, the most obvious being the alteration of the mechanisms that regulate the balance between proliferation and cell death.

Dual role of TGF-beta

The objective of the study is to dissect the response of tumour cells to TGF-beta when aborts the EGFR via. TGF-beta is involved in the regulation of several cellular processes. With regard to tumors, has demonstrated that it has a contradictory dual role. On the one hand, in initial States induces programmed cell death, so you have a suppressing tumor growth function, but in more advanced States favours cell invasion and migration and, It is therefore, metastasis.

The cancellation of the EGFR pathway was pharmacologically and silencing their expression through the use of RNA interference with the same results. Inhibition of the EGF receptor not only attenuates cell proliferation, but it also increases the suppressing function of TGF-beta, Therefore it might be a therapeutic target for liver cancer. Now well, This brake on the growth of tumor cells does not occur in all cases. The cell lines that have certain genetic disorders (in the operation of the TGF-beta or the proteins involved in the EGFR signaling pathway, but subsequent to the receiver steps) do not respond to EGFR inhibition and tumor cells continue to grow.

The Coordinator of the study, Isabel Fabregat, emphasised that you to make "a good personalized medicine is necessary to analyze the molecular biology of tumor cells of the patient", their phenotype and your background of genetic and epigenetic; "so you can predict which patients are likely to respond effectively to the treatment and what not".

The study has been done in hepatocellular carcinoma cell lines and in the coming months will begin a study with an experimental model in mice.

The article reference

Box L., Sancho P., BERTRAN (E)., Fabregat I. Dissecting the effect of targeting the epidermal growth factor receptor on TGF-B-induced-apoptosis in human hepatocellular carcinoma cells, Journal of Hepatology (2010), DOI: 10.1016/j.jhep.2010.10.041