Growing tiny tumours in the lab could help treat cancer

ALMOST half a century after Richard Nixon declared war on cancer, there has been plenty of progress. But there is still no cure.

One reason is that “cancer” is an umbrella term that covers many different diseases. Although the fundamental mechanism is always the same—the uncontrolled proliferation of cells—the details vary enormously. Leukaemia is not the same as colon cancer. Even within a particular type of cancer, one patient’s disease will differ from another’s. Different mutations, for instance, will affect different genes within a tumour. The result is that cancer can be frustratingly difficult to treat.

Medicine, though, is getting better at accounting for these differences. In a paper just published in Nature Medicine, a team led by Meritxell Huch, a biologist at the Gurdon Institute, a cancer-research centre at the University of Cambridge, describes a technique that could, one day, help doctors design bespoke treatments for their patients, tailored to the precise characteristics of the cancers they are suffering from.

Dr Huch and her colleagues work with “organoids”, tiny replicas of full-sized organs that can be grown in the lab. The ability to build organ-like structures outside a living body, from retinas to kidneys and even brain tissue, holds a great deal of promise for medical research. But Dr Huch’s twist was to grow not organs, but the tumours that afflict them.

She and her team took cancerous cells from eight patients suffering from liver cancer. That is the fifth most frequent cancer in men around the world and the eighth most frequent in women. But its high mortality rate makes it the second most common cause of cancer deaths worldwide, behind only lung cancer. By immersing the cells in a specially developed culture medium designed to promote the survival of cancerous cells but not healthy ones, the researchers were able to persuade their samples to grow into tiny “tumouroids” about 0.5mm across.

Cancerous cells can already be cultured in test tubes, where they are available for poking and prodding by researchers. But, says Dr Huch, when researchers extract such tissue they often bring healthy cells along with it. That can complicate genetic analysis of the tumours, by mixing healthy DNA with the mutated sort. Because tumouroids contain only cancerous cells, analysing them should be easier.

A more significant benefit is that tumouroids replicate the structure of the tumours from which they are derived in a way that ordinary cell cultures do not. Cells in a living organism are often not symmetrical. The cells that make the intestines, for instance, need to know which side faces into the intestine and which side faces the rest of the body. That, in turn, means different genes are expressed in different parts of a cell. In a conventional cell culture, much of this structure is lost. But Dr Huch’s tumouroids preserve it, making them a much more faithful reproduction of the cancer from which they are derived.

Having copies of a tumour in a dish makes it easier to cDr Huch and her colleagues work with “organoids”, tiny replicas of full-sized organs that can be grown in the lab. The ability to build organ-like structures outside a living body, from retinas to kidneys and even brain tissue, holds a great deal of promise for medical research. But Dr Huch’s twist was to grow not organs, but the tumours that afflict them.

She and her team took cancerous cells from eight patients suffering from liver cancer. That is the fifth most frequent cancer in men around the world and the eighth most frequent in women. But its high mortality rate makes it the second most common cause of cancer deaths worldwide, behind only lung cancer. By immersing the cells in a specially developed culture medium designed to promote the survival of cancerous cells but not healthy ones, the researchers were able to persuade their samples to grow into tiny “tumouroids” about 0.5mm across.

Cancerous cells can already be cultured in test tubes, where they are available for poking and prodding by researchers. But, says Dr Huch, when researchers extract such tissue they often bring healthy cells along with it. That can complicate genetic analysis of the tumours, by mixing healthy DNA with the mutated sort. Because tumouroids contain only cancerous cells, analysing them should be easier.

A more significant benefit is that tumouroids replicate the structure of the tumours from which they are derived in a way that ordinary cell cultures do not. Cells in a living organism are often not symmetrical. The cells that make the intestines, for instance, need to know which side faces into the intestine and which side faces the rest of the body. That, in turn, means different genes are expressed in different parts of a cell. In a conventional cell culture, much of this structure is lost. But Dr Huch’s tumouroids preserve it, making them a much more faithful reproduction of the cancer from which they are derived.

Having copies of a tumour in a dish makes it easier to conduct experiments on them. By comparing the genomes of their tumouroids to those of healthy tissue, the team discovered unusually high levels of activity among some genes in the tumour cells. Nineteen of the 30 most over-active genes were already associated with a poor prognosis, but 11 were new genes for which such a link had not been suspected. They also used the tumouroids to test 29 sorts of anti-cancer drugs, some of which are still in development. For one, an inhibitor of a type of protein vital for tumour growth, the researchers have managed to publish the first evidence suggesting that it might indeed be effective.

The ability to grow accurate replicas of real tumours should help the hunt for better cancer drugs more generally. Compared with treatments for other diseases, many cancer drugs fail to make it past even the early stages of clinical trials, partly because of the difficulty of producing accurate models of the disease on which to do preliminary testing. Dr Huch hopes her tumouroids might have direct clinical applications, too. The goal, she says, would be to take a patient with liver cancer, grow copies of his tumour in a lab, and then test several different drug candidates at once to find the most effective. Because tumouroids faithfully replicate the cancers from which they are derived, a drug that works in the test tube should work in the patient as well. As any general will tell you, knowing your enemy is half the battle.

 

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