Genome editing to determine the role of oestrogen receptor beta in MTC

Professor Chris McCabe (Institute of Biomedical Research, University of Birmingham)

Medullary thyroid cancer (MTC) can be very aggressive and fatal with a five year survival rate in advanced disease of just 25%. To develop new treatments and improve survival rates we first need to understand what changes have occurred to normal thyroid cells to make them aggressive and cancerous. Typically cancer cells contain changes to genes, i.e. so called “mutations”, which disrupt their function. This can lead to a loss in certain abilities of the cell such as in controlling how quickly it grows and divides. The overall aim of this project is to gain sufficient understanding of key gene changes in MTC tumour cells to enable new drug treatments to be developed that interfere with the action of these mutations and so prevent tumour progression.

We recently made a significant discovery and identified novel mutations in the gene for oestrogen receptor beta (ERb) in MTC individuals. ERb has previously been reported to have an important role in controlling the growth of cancer cells. To better understand the role of these novel ERb mutations in cancer we plan to mimic the situation in MTC individuals by modifying cells so that the gene for ERb is turned off (or disabled). Once this is achieved we will assess how these modified cells respond to conditions associated with cancer development. For example, we will investigate the properties of modified cells growing in a low oxygen atmosphere. This is important as human solid tumours are deprived of oxygen which can alter ERb activity and also lead to resistance to anticancer chemotherapy. In addition, we will determine how the growth of modified cells is affected by oestrogen, a hormone that stimulates growth of cancer cells via oestrogen receptors.

An exciting aspect of this project is that we will also use these modified MTC cells to screen and identify new drugs capable of blocking the cancer promoting effects of ERb in MTC tumours. This should help us in our overall long-term goal of developing new and more effective treatments for individuals with MTC.

More About Professor McCabe

The research of the McCabe group focuses on assessment of the role of the proto-oncogenes PTTG and PBF in thyroid, breast and colon tumours; in vitro and in vivo models exploring gene function; gene expression in multiple tumour models; mechanisms of aneuploidy and genetic instability; the action of the sodium iodide symporter NIS in thyroid tumours.

The McCabe group currently holds funding from the Medical Research Council, the Royal College of Surgeons, BBSRC, NIHR etc. Members of the group include a Consultant Clinician, a non-clinical Lecturer, an MRC Senior Research Fellow, a Surgical Fellow, 2 MRC funded PhD students, a Saudi Government PhD Student and an MRC technician.

Chris McCabe is Chair of the Wellcome Trust Basic Science Committee, and Chair of the Science Committee for the Society for Endocrinology.

Outside of science, Chris McCabe has published 9 novels under 2 pseudonyms, has written for newspapers including the Guardian and the Independent, and is a script editor for numerous factual TV series.