A drug that stops the spread of cancer has been developed, with scientists identifying the cells responsible for initiating and promoting metastasis. While the drug has only been tested on mouse models, researchers are hopeful the discovery will have widespread applications for future cancer treatments.
Metastasis the process through which cancer spreads from one part of the body to another. It is one of the aspects of the disease that makes it so deadly – indeed, it is the reason behind 90% of human cancer deaths. The process by which cancer spreads is extremely complex. The cells that trigger metastasis are not known, so the development of therapies to prevent it is challenging.
However, a team of researchers led by Gloria Pascual of the Institute for Research in Biomedicine (IRB Barcelona) has now found these cells, and shown how they can be used to stop the spread of cancer.
In a study published in the journal Nature, the team found a specific protein – CD36 - in the membranes of tumour cells that are responsible for taking up fatty acids (a receptor). The team discovered CD36+ cells in samples of human oral carcinoma (oral cancer).
When CD36 was absent from the tumours, they did not develop metastasis. When it was added, the tumours became metastatic.
Researchers then looked at CD36 in mouse models of oral, melanoma and breast cancer. After treating them with antibodies to block the receptor, metastasis was either significantly reduced or totally eliminated. Furthermore, metastases already present shrunk or disappeared. Where matastases was already established, the treatment removed it in 20% of the cases, and reduced it in between 80-90% of the remainder. There were no significant side-effects observed.
Cancer metastasis dependent on fat?
Because CD36 is responsible for the uptake of fatty acids, the researchers looked at what role fat intake has on the spread of cancer. To do this, they provided one group of mice with a high-fat diet and inoculated them with oral cancer. In the control group, 30% went on to develop metastasis, compared to 80% of the high-fat group. This indicates a high-fat diet increases the risk of metastasis.
Aznar Benitah said: "In mice inoculated with human tumour cells, there appears to be a direct link between fat intake and an increase in metastatic potential through CD36. More studies are needed to unravel this intriguing relationship between diet and metastasis, above all because industrialised countries are registering an alarming increase in the consumption of saturated fats and sugar.
"Fat is necessary for the function of the body, but uncontrolled intake can have an effect on health, as already shown for some tumours such as colon cancer, and in metastasis, as we demonstrate here."
Further analysis showed metastasis is also dependent on CD36 in ovarian, bladder and lung cancer. Findings indicate there could be a general mechanism that underlies metastasis – and treatments that block CD36 could be key to stop the spread of cancer.
"Although we have not yet tested this in all tumour types, we can state that CD36 is a general marker of metastatic cells, the first marker I know of that is generally specific to metastasis," said Salvador Aznar Benitah, head of the Stem Cell and Cancer Lab at IRB Barcelona.
"We expect this study to have a big impact on the scientific community and to further advances in metastasis research, and we hope to be able to validate the potential of CD36 as an anti-metastasis treatment. Things like this don't happen every day."
The team is now working with researchers in the UK to develop antibody-based treatments that work against CD36 for a range of cancers. If successful, they believe a new drug could be available in five to 10 years.