What if doctors could build a model of your organs inside a laboratory, then use it to predict whether or not you will develop cancer – and when? It sounds like the makings of a science-fiction film, but cancer researchers may be closer to that landmark than we realise.
As recently as 25 years ago, few experts fully understood the genetic basis for breast and ovarian cancer. Doctors noticed that both illnesses sometimes seemed to run in families. But they had little idea why this was happening – or what, if anything, could be done about it.
Then in the 1990s came the discovery of the BRCA1 (breast cancer 1) gene; closely followed by the discovery of the BRCA2 (breast cancer 2) gene. It revolutionised our approach to hereditary cancers, expanding treatment and prevention options and probably saving thousands of lives.
And now, scientists have made another huge leap, with an innovative study published by scientists in Los Angeles, this week. Researchers used a technique involving pluripotent stem cells, which essentially allows scientists to take cells “back in time” and “forward again” to see how they develop, explains Dr Clive Svendsen, executive director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute, and senior author of the study.
Using cells from the blood of healthy women and women who had inherited a faulty BRCA1 gene and developed ovarian cancer, they developed organoids (a simplified, miniature replication of an organ) of fallopian tube tissue, where research indicates ovarian cancer actually begins. For the first time, scientists could observe the impact of such faulty genes up close.
Over the course of six months, they watched as the organoids from the BRCA1 patients began to show “enhanced structural abnormalities”, indicating cancer, according to the study published in the journal *Cell Reports*.
“It’s so exciting,” says Dr Svendsen. “It’s unbelievable that we can now simulate what would happen in a human in diseases like cancer, and then treat it in a dish before you even have it. We could do this when a woman's 10 years old – it doesn't matter when we take the cells. It's a predictive model.”
How do BRCA genes work?
Everybody has a BRCA1 and BRCA2 gene. They are known as ‘tumour suppressors’, because they protect us from cancer by correcting DNA damage inflicted when cells divide. But about one in 450 people have mutations in these genes.
“If you've got a faulty copy of one of those genes, it's not able to do its job, it's not able to stop the cells dividing, and that can lead to cancer,” explains Karis Betts, health information manager at Cancer Research UK.
According to US figures, about 50 in every 100 women with a faulty BRCA gene will develop breast cancer by the time they turn 70, compared to about seven in 100 among the general population. About 30 in 100 will develop ovarian cancer, compared to fewer than one in 100 in the general population.
Men are slightly less badly affected, but are still at an increased risk. About 25 in 100 men with a faulty BRCA gene will develop prostate cancer at some point in their lives. About seven in 100 men with a faulty BRCA gene will develop breast cancer.
The Angelina Jolie effect
BRCA genes burst into the public consciousness in May 2013, when Hollywood actress Angelina Jolie revealed that she had undergone a double mastectomy (an operation removing both of her breasts) in order to prevent breast cancer.
Jolie had previously tested positive for a faulty BRCA1 gene. Jolie’s mother, humanitarian Marcheline Bertrand, died in 2007, aged 56, following an eight-year illness with breast and ovarian cancer. Jolie’s aunt and grandmother both also died of cancer.
In the months after news of Jolie’s surgery broke, there was a large increase in the number of women in the UK visiting their doctor to enquire about genetic breast cancer tests. Referrals for BRCA screening more than doubled, according to a study led by Prof Gareth Evans and published in the journal Breast Cancer Research. It was dubbed the “Angelina effect”.
What is the potential for this new study?
Currently, a genetic test can tell you whether or not you have a faulty BRCA gene – but it can’t tell you much beyond that. The organoid technique used in Dr Svendsen’s trial – in which human organ tissue is replicated inside a lab – could in the future revolutionise our approach to cancer, giving you a personally tailored prediction of whether or not you will actually develop cancer, he says. This could come years or even decades in advance. It could also allow scientists to test treatments on organoids before exposing patients to them.
“By replaying variant cancer over and over again, we can keep replaying the [process], find out what caused it, and then develop drugs that stop it from happening,” Dr Svendsen says.
Imagine a young woman who finds out she has inherited a faulty BRCA gene. Currently, she’s told there’s roughly a 50-50 chance she’ll develop breast cancer before she’s 70, and she is faced with the decision of whether to undergo a mastectomy. The operation would seriously reduce her risk of developing breast cancer – but it’s a procedure that many women consider intense and life-changing, and one she might not even need. There’s also the question of timing: she might prefer a mastectomy when she’s older, once she’s finished having children and finished breastfeeding. Or she might want the operation as soon as possible.
In the future, Dr Svendsen says, that young woman could be given a specific prediction, tailored uniquely to her. Her blood could be taken, and her cells used to generate a lab-grown model of her organ tissue. Then, scientists could essentially fast-forward the ageing process, watching in a laboratory to see whether or not cancer develops. This could give her a much clearer indication of what, if any, steps she needs to take – and when.
There are limitations, of course. It’s a new technology, with many questions yet to be answered. Dr Svendsen stresses that more research is needed to confirm the predictive power of this model.
But it’s certainly an exciting development – and could carry ramifications for our approach to other cancers, too. “Models using this technology are going to become more and more prevalent,” he says, promising the possibility "to prevent disease rather than treat it.”