'Encouraging' skin cancer discovery: P-Rex1 plays key role in spread of malignant melanoma

Unlike most other cancers, malignant melanoma is disproportionately higher in younger people than in other age groups. More than two young adults (aged 15-34) in the UK are diagnosed with the disease every day.

While survival rates have been improving for the last 25 years and are now amongst the highest for any cancer, malignant melanoma still causes around 46,000 deaths worldwide each year -- around 2,560 of those in the UK. The high death rate is due to cancer cells breaking away from the original tumour and spreading or 'metastasising' to other organs like the brain, causing them to fail. It is its ability to metastasise that makes cancer so dangerous.

Using a grant from the Association for International Cancer Research (AICR), Professor Owen Sansom and his team at the Beatson Institute for Cancer Research have shown that a specific gene (P-Rex1) must be present before malignant melanoma can spread.

In research just published in the scientific journal Nature Communications, Professor Sansom and his colleagues demonstrated the key role that P-Rex1 plays in the spread of malignant melanoma.

Using mice models which mirror the common human genetics of melanoma, the researchers found that if P-Rex1 was absent from the cells, the melanoma tumours were unable to spread. Further investigation enabled them to decipher the exact mechanism that P-Rex1 uses to drive metastasis and which is blocked when P-Rex1 is removed.

They then clearly confirmed that human melanoma samples, taken from patients' tumours, contained raised levels of P-Rex1.

Said Professor Sansom: "By contrast P-Rex1 is not present in most other normal human cell types, pointing up its suitability as a gene to be 'switched off' with chemotherapeutic drugs, as there are unlikely to be any unwanted side effects on nearby healthy cells.

"As malignant melanoma is resistant to many forms of chemotherapy, these findings are encouraging. Earlier studies using cancer cell lines implicated P-Rex1 in prostate, breast and ovarian cancer but this is the first time it has been shown to be involved in the metastasis of melanoma in mice models as well as being present at high levels in human tumours and cell lines where it drives invasion into surrounding tissue.

Dr Lara Bennett, scientific communications manager for AICR said Professor Sansom's discovery was an excellent example of how basic research, like that funded by AICR, can help form the building blocks for future treatments.

"Although it is early days and more research is needed, if drugs could be designed to block the effects of P-Rex1, melanoma could be prevented from metastasising," she explained. "This would ensure it remained on the surface of the skin where it could easily be removed through surgery, leading to higher survival rates."

Malignant melanoma incidence rates in Britain have quadrupled over the last thirty years with around 11,760 cases diagnosed in the UK each year and almost 200,000 worldwide.

"If malignant melanoma is caught sufficiently early -- while still only a very thin tumour in the top layers of the skin -- survival rates are much higher," said Dr Bennett.