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The most important indicator of whether an individual will overcome cancer is whether or not the tumour has metastasised – spread beyond its original site. So researchers are investigating the factors that drive metastasis, and the results look set to improve prognosis and treatment.
A particularly promising approach, being opened up by David Lyden and Hector Peinado at Weill Cornell Medical College in New York, focuses on tiny bodies called exosomes that break off from cancer cells. Exosomes are vesicles: microscopic bubbles full of proteins and genetic messenger molecules.
“Tumours can send out these bubbles of information and signals that other cells, such as bone marrow cells, then receive and act upon,” says Lauren Pecorino, a cancer biologist at Greenwich university in London.
“This work supports the ‘seed and soil’ theory of metastasis proposed by Stephen Paget 120 years ago,” she says. In other words, the exosomes create fertile soil in specific sites elsewhere in the body, which will then be receptive to seeding by any cancer cells shed from the tumour.
Healthy exosomes work as an intercellular signalling and communications system, says Peinado. For example, they summon cells to a site of injury to help in the healing process.
But cancer perverts this process. Lyden, Peinado and colleagues have shown that tumours give off a different type of oncogenic exosome, packed with extra biomolecules that create a congenial nest for metastatic cancer cells. The more exosomes a tumour produces, the more quickly it metastasises.
Experimental results published in Nature Medicine confirm that the prospects of surviving melanoma depend on exosome activity. “Now oncologists can tell one lot of patients they are unlikely to metastasise and another lot that they are likely to metastasise, so they need to come to the clinic more frequently for a check-up after their tumour has been removed,” Lyden says.
Fortunately, there is a good chance that understanding exosomes will lead to treatments that reduce the risk of metastasis. The Weill Cornell team has shown that a signalling protein called MET plays an important role in the process – and pharmaceutical companies are already developing drugs that target MET.
These are heady times in cancer biology, with scientists making rapid progress on several fronts. Pecorino, who is an author of two books on cancer but not directly involved in the exosome work, has no doubt about its significance: “I would describe it as being the most far-reaching discovery in recent cancer research history.”