The spread of cancer could be stopped – with injections of oxygen, according to new research.
The trigger for the disease spreading is when the gas is cut off – a discovery that opens the door to better treatments.
Experiments on mice with breast tumours found they lived longer after the oxygen supply was increased.
It sheds fresh light on ‘metastasis’ or the spread of the disease, in which cells break off from the original site and migrate through the body. The process dramatically reduces chances of recovery – and has baffled experts for decades.
Preventing it is the ‘holy grail’ of research – turning cancer from a killer to a chronic illness.
Little was known about why these clusters of circulating tumour cells (CTCs) leave in the first place. Lack of oxygen has now been identified as the trigger. It offers hope of improved strategies, said lead author Professor Nicola Aceto.
This may include boosting the formation of blood vessels – which would carry more oxygen in. The technique, called proangiogenic therapy, worked in the rodents.
She likened it to people in a packed bar or club struggling for breath – and going outside to breathe in fresh air.
Her team analysed the amount of oxygen inside the animals’ human-like tumours, the detachment of CTCs and their molecular and cell biological properties.
They found different areas are supplied with different levels of the gas. Cancer cells with a lack of oxygen cropped up where there were fewer blood vessels.
This included the core as well as peripheral areas. Clusters that had separated also had less oxygen – showing they depart if they do not receive enough.
Prof Aceto, of Basel University, Switzerland, said: “It is as though too many people are crowded together in a small space. A few will go outside to find some fresh air.”
Further tests showed oxygen-deprived CTC ‘mobs’ are more dangerous than those with normal content. They spread faster – and the mice died sooner.
Prof Aceto said: “If a tumour does not have enough oxygen these CTC clusters, which have a particularly high potential to develop metastases, will break away.”
The findings published in Cell Reports inspired the researchers to stimulate blood vessel growth in the mice with drugs.
When they injected them through their tail vein with a blood vessel boosting protein found in arteries it increased oxygen in the tumours.
As expected, the number of separating CTC clusters dropped, the mice formed fewer secondary tumours and survival increased.
But, at the same time, the primary tumour increased in size significantly.
Prof Aceto said: “This is a provocative result. If we give the tumour enough oxygen, the cancer cells have no reason to leave and metastasise. On the other hand, this accelerates the growth of the primary tumour.”
The next challenge is to transfer the results to the clinic where the characteristics of tumours vary from patient to patient.
Prof Aceto said: “But we speculate substances that improve oxygen supply to the tumour can inhibit the formation of metastases in breast cancer, alone or in combination with other agents.”
She is excited that the method will be effective for many forms of the disease.
Prof Aceto said: “CTCs are considered to be metastatic precursors in several cancer types, including breast cancer. But the mechanisms that lead to their generation from a solid tumour mass are poorly understood.”
The results were confirmed in 1,746 patients with advanced breast cancer. Blood tests showed clusters of oxygen lacking cells predicted earlier spread.
Scientists once tried to starve tumours of the gas, believing a more stable blood supply would only help the cancer spread.
In the last decade or so interest has focused more on the potential of increasing it.
One Oxford University found this made chemotherapy more effective.
Added Prof Aceto: “We speculate therapies aimed at reducing lack of oxygen hypoxia, alone or in combination with anti-cancer agents, may provide a new opportunity to blunt the metastatic spread of cancer in breast cancer patients.”