EACR 21, 26—29 June 2010, Oslo
Interview with Professor Manel Esteller (Cancer Epigenetics and Biology Programme (PEBC), Barcelona, Spain)
The role of epigenetics in cancer therapy
Why are epigenetics important in cancer?
Nowadays we know that cancer is a genetic disease and also an epigenetic disease; genetics because it has mutations and epigenetics because it has a deregulation of gene expression. We know that between normal cells and cancer cells there are thousands of genes that are down-regulated or overexpressed and this is not by mutation, it’s because there are chemical markers that are wrong and different between a cancer cell and a normal cell.
Epigenetics, it’s a good path for epigenetics and this is the path that makes us express the right gene in a neuron or in a cell from the mouth and not vice versa but the wrong path is when the gene becomes silenced or inactive in a cancer cell. The genes that become inactive in a cancer cell are tumour suppressor genes and these are critical genes because their normal function is to inhibit the growth of cancer cells.
This is a good part of the story, also here, because now there are drugs that have been approved and what they do is they restore the expression of these genes. These drugs have been successful in the treatment of certain types of leukaemias and lymphomas.
What are you working on?
So my lab is working in finding new genes that undergo epigenetic inactivation in cancer cells and also testing in a pre-clinical manner these drugs to show that they are able to inhibit the growth of cells in culture and in mice. We also have an interest in developing epigenetic biomarkers. For example, we show markers based in epigenetics that are able to predict responses to chemotherapy in glioma and breast cancer.
What are these markers?
The best example of an epigenetic marker that has reached the clinic is the silencing inactivation of the enzyme called MGMT. If in a glioma, in a brain tumour, you have MGMT epigenetic inactivation, this is a tumour that should receive a particular drug – timodal. But if you have this enzyme active, unmitigated, then you should receive another treatment. We have now a further example showing that other genes in breast cancer are also able to predict the use of one drug or another.
Are there examples being used in breast cancer?
In breast cancer there has been an example of how solid tumours are more resistant, so far, to epigenetic drugs than a pathological malignancies. The pathological malignancies in those types were able to reprogram the cancer cells, just changing the epigenetics, changing the regulation of the genome. Solid tumours are a lot harder in this case but the first clinical trials using histone deacetylase inhibitors, H-stack inhibitors, are undergoing to show if these drugs are effective as a treatment of breast cancer.
Are there histone deacetylase inhibitors being used at the moment?
There are different H-stack inhibitors used, they have been, so far, only approved for the treatment of different forms of lymphoma, like cutaneous lymphoma, Hodgkin’s lymphoma and T lymphoma. These drugs have shown an important success in those settings.