Scientists created a novel drug which blocks production of the protein lysyl oxidase (LOX), known to contribute to tumour growth and spread, and were also able to identify the mechanism behind this action.
'We knew that LOX had a role in cancer's spread round the body, but to discover how it also appears to drive the growth of breast cancer cells is a real game changer,' said Professor Caroline Springer of The Institute of Cancer Research and co-lead of the study, which was published in Nature Communications.
LOX helps to shape the extra-cellular matrix, the tangled mesh of molecules that surrounds and supports cells. Previous research had indicated this function of LOX makes it easier for cancer cells to spread, and high levels of LOX in tumours are also associated with poorer patient outcomes.
Researchers at the Institute of Cancer Research in London and the University of Manchester were able to demonstrate that blocking production of LOX reduces the amount of epidermal growth factor receptor (EFGR) on cell surfaces.
Under normal conditions, EGFR helps cells know when to grow and divide. However, in various cancers EGFR is often over-produced or mutated and causes cancer cells to grow faster. The results show that LOX can increase the 'grow' signal of cancer cells.
Using mice which spontaneously develop breast cancer, scientists also showed that tumour size and numbers were reduced when the LOX gene was removed. By creating a new compound which potently inhibits LOX, the authors also showed they could reduce the growth of tumours with no side effects.
The new potential drug, currently referred to as CCT365623, is a modified and improved version of the sole earlier LOX drug, which was chemically unsuitable to be given as a medication. The next step will be to develop an inhibitor suitable for clinical trials.
'This research in mice is exciting because it not only reveals new details of how breast cancer grows and spreads, but it could lead to a completely new way to stop these processes in patients if proven in people,' said Dr Justine Alford from Cancer Research UK, who was not involved in the study.
This could help improve outcomes for patients, since cancer that has spread is harder to treat. LOX is also thought to play a role in a number of other cancers, so this research could also have applications beyond breast cancer.'