Does the answer lie within…? Using patients’ proteins to target breast cancer
23 May 2014
Breast cancer remains the most common type of cancer in the UK, with women at a 1 in 8 lifetime risk of being diagnosed with this disease. In 2010 alone, more than 49,500 women were diagnosed (equivalent to 136 women per day) and approximately 400 men1. Here, Raffaella Facchini describes a recent collaborative study including researchers at the WIMM which could help to develop novel diagnostic and therapeutic strategies for breast cancer.
Despite recent improvements in treatment regimes and genetic testing, there are a significant number of individuals who do not respond to current therapies for breast cancer. This means that much more work needs to be done in order to understand how this disease develops, why it affects specific people so differently and to identify potential new targets which will lead to more effective treatments.
A recent collaborative study between groups based at the University of Huddersfield, University of Liverpool and in Adrian Harris’ lab within the Department of Oncology at the WIMM has explored how two proteins present in the most dangerous type of tumour found in breast cancer patients could be used to subclassify patients, and potentially develop novel, more targeted therapies.
During cancer progression, the normal behaviour of a cell is altered and it begins to divide uncontrollably, forming a tumour. As the tumour grows, parts of it become deprived of oxygen due to its increased size and poor quality blood vessels. Normally, cells require oxygen to produce energy, but when there is limited oxygen available, cells turn to an alternative pathway for energy production that requires the uptake of more sugars. This pathway involves two key proteins: carbohydrate responsive element (ChREBP), and Glut-1. Glut-1 allows the cells to take up more sugars, and ChREBP regulates the process that allows the cells to store any leftover sugars which may be used “on demand” to support cell division.
By comparing samples from breast cancer patients to samples from patients with other types of cancer and in normal tissues, the researchers found that the Glut-1 and ChREBP proteins could be identified at much higher levels in patients with aggressive forms of breast cancer.
The authors speculate that the role of Glut-1 and ChREBP in development of breast cancer is to give cancer cells two options for energy production. Which option they take depends upon whether or not cells have enough oxygen. Therefore, whilst increased expression of Glut-1 allows cells in the deepest parts of the tumour to continue to grow even in the almost complete absence of oxygen, ChREBP in contrast is expressed in circumstances where more oxygen is available. ChREBP activates the expression of the proteins that, once normal oxygen levels have been restored, will continue to support the uncontrolled growth of the tumour. Together, this switching between functions controlled by Glut-1 and ChREBP could explain why these two proteins are present in some of the most serious and threatening types of breast cancer.
Whilst further research is required to determine how to successfully target these two proteins, these results are a positive step forward. Defining how tumours differ within patients at the most fundamental level of cells and proteins will help to develop specific, targeted therapeutic strategies, and holds the key to developing effective treatments for patients suffering not only from breast cancer, but also other cancers.