Scientists at The Institute of Cancer Research (ICR) have found an important new drug target for advanced bowel cancer that could also be used to identify tumours that will respond to a drug already used in other cancers.
Dr Janine Erler and colleagues earlier discovered the enzyme lysyl oxidase (LOX) plays a key role in the spread of breast cancer, and suspected it may also be involved in metastasis of other cancers.
In the latest study, published today in the Journal of the National Cancer Institute, Dr Erler’s team confirmed LOX was also important in bowel cancer growth and spread. They found cell growth increased in tumour cells with high levels of LOX, while low levels of LOX led to limited cell growth.
The team further showed that LOX was activating a molecule called SRC to promote cancer growth and spread. A drug called dasatinib is known to block SRC function and is already being used to treat leukaemia patients.
In laboratory tests, Dr Erler’s team found dasatinib reduced bowel cancer cell growth by inhibiting the effects of LOX.
“Our findings have revealed two potential new avenues for combating advanced bowel cancer – either with existing SRC inhibitor treatments or with drugs currently being developed to target LOX,” Dr Erler says.
“We are looking forward to future clinical trials to see whether these drugs could benefit patients with advanced bowel cancer, who currently have few treatment options.”
The research also showed that a test for levels of LOX expression could be used to recognise cancers whose SRC molecules are highly activated, therefore identifying patients most likely to benefit from treatment with dasatinib.
The study was supported by the Medical Research Council, the ICR, Cancer Research UK, and a Seeding Drug Discovery award from the Wellcome Trust.
Professor Malcolm Dunlop of the Medical Research Council (MRC) says: "Finding a way to prevent metastatic spread of tumours is crucial if we are to reduce the number of deaths from bowel cancer. The discovery that controlling the enzyme LOX could influence colorectal cancer cell growth is very encouraging. Supporting excellent research which answers fundamental questions about how cancer cells manifest in our body is vital if we are to see new and better treatments in the clinic."
Dr Julie Sharp, senior science information manager at Cancer Research UK, said: "Cancer spread causes most deaths from the disease and is a key challenge for our doctors and scientists. This research sheds light on how bowel cancer spreads and offers new avenues that scientists can exploit to try and treat people with advanced disease more effectively."
Bowel cancer is the third most common cancer worldwide, causing 529,000 deaths annually. Metastatic bowel cancer currently has few treatment options and a poor prognosis.
"The Role of Lysyl Oxidase in SRC-dependent Proliferation and Metastasis of Colorectal Cancer” publishes online Monday 31 January 2011 in Journal of the National Cancer Institute.
The Institute of Cancer Research (ICR)