A GENETIC analysis of cancers is challenging long-held ideas about the disease. It could one day help more patients to survive, and spare others needless treatment.
The most deadly tumours are those that can spread to other places in the body or 鈥渕etastasise鈥�. Once these secondary tumours form, it is often too late to save a patient.
The received wisdom is that metastatic tumours develop in a series of steps. First a few cells begin to divide out of control and form a primary tumour. Then rare cells within the tumour mutate further and acquire the ability to spread around the body.
Advertisement
Now a team led by cancer specialist Sridhar Ramaswamy of the Whitehead Institute in Boston is developing a genetic test that identifies which tumours have the ability to spread. The studies show that many tumours can do this right from the start.
At the moment, after a patient has had a primary tumour removed, doctors can only make an educated guess about whether they are likely to develop secondary cancers, based on CAT scans and the size and appearance of the tumour. 鈥淐urrent methods for determining which patients are at highest risk are crude,鈥� Ramaswamy says.
If metastatic tumours could be identified reliably straight after surgery, patients at risk of secondary cancers could be given aggressive treatments such as chemotherapy straight away. Conversely, patients who do not need such treatment could be spared its unpleasant side effects. And Ramaswamy has shown that he can tell the two groups apart.
His team used 鈥済ene chips鈥�, or microarrays, to look at thousands of genes in tumours taken from people with lung, breast or prostate cancer to see which were switched on. From this the researchers drew up a profile involving 17 genes that seemed to be characteristic of metastatic tumours. Next, they used the profile to classify tumours from over 300 cases. They showed it could indeed predict the chances of patients developing secondary cancers (see Graph).
The team will have to look at many more samples to confirm that the test is accurate, Ramaswamy cautions. It may prove necessary to extend the profile to include more genes, for instance. So it will be several years before doctors can use the test.
Meanwhile, the results are the first firm evidence that some tumours are capable of metastasis from the moment they appear. Most doctors assume that the larger a tumour is, the greater the chances of some cells becoming metastatic. 鈥淏ut that may not be the case,鈥� Ramaswamy says.
Surprisingly, none of the 17 genes is known to play a role in metastasis. They may just be markers for other changes. 鈥淏ut I don鈥檛 think that matters,鈥� says Lawrence Young, director of the Institute for Cancer Studies in Birmingham. What鈥檚 important is that such a test could help doctors treat a patient better. 鈥淔or all we鈥檝e discovered about cancer in recent years, there鈥檚 been precious little that鈥檚 translated into anything useful.鈥�
He says gene chips could help doctors choose the right drugs for patients, besides identifying those at most risk. The challenge is to make them cheap and reliable.