A ‘switch’ that fuels the spread of prostate cancer has been discovered.
Turning it off destroyed tumours in lab dishes – and mice, say scientists.
An American research team targeted an enzyme known as CDK7 – which they described as the “on/off switch”.
Blocking it killed the most agressive type of the disease known as metastatic castration-resistant prostate cancer (CRPC).
It could lead to a cure for the deadliest forms that are resistant to current medications.
Drugs known as CDK7 inhibitors are already being tested in early clinical trials for other cancers – including leukaemia and those of the lung, brain and breast.
Study senior author Professor Irfan Asangani, a cancer biologist at the University of Pennsylvania, said the latest findings show the need to try them for prostate cancer.
He said: “Blocking CDK7 sets off a chain reaction that results in the death of prostate cancer cells that have spread and are resistant to standard therapies.”
His team found it controls a gene called Med1 along with an androgen receptor (AR), or male hormone, to drives the growth of prostate cancer.
The study, published in the journal Cancer Discovery, showed tumour cells in mice were destroyed when it was switched off.
Prof Asangani said: “We know AR does not work alone; that it needs Med-1 as its partner.
“Our study found a way to turn off Med1, leaving AR without its co-pilot which means the cancer cannot grow and the cells eventually die.”
Using a compound to turn off CDK7 led to the death of CRPC cells in both the lab setting and in animal models.
There were also few side effects since healthy cells are not harmed by the loss of Med1, meaning only the cancerous ones die off.
Prof Asangani added: “Our theory is these cancer cells are addicted to Med1 and AR but other cells are not, so we are essentially cutting them off from their addiction.”
Androgen deprivation therapy is a standard approach to treating prostate cancer. But most patients will eventually become resistant to it, allowing the tumour to spread.
There are two drugs approved by the US Food and Drug Administration for these cases, but they produce no long-term survival benefit.
Male hormones, or androgens, remain the power station of CRPC, so taking away their function is critical.
But the disease is resistant to drugs that target them directly. So a new approach is needed, said Prof Asangani.
These tumours do not have additional mutations or other genetic over expression. The team diverted their attention to Med1, or “AR’s co pilot” – which is regulated by CDK7.
Almost 43,000 men were diagnosed with prostate cancer in England and Wales between April 2016 and March 2017.
In England alone, the proportion whose cancer was metastatic – meaning it had reached other organs or tissue – was 16 per cent.
Prostate cancer claims about 11,500 lives in the UK every year – more than breast cancer.
It is the second most common cause of cancer death among men, behind lung cancer.
Prof Asangani added: “Metastatic castration-resistant prostate cancer (CRPC) is a fatal disease, primarily driven by the androgen receptor (AR).
“First-line CRPC treatments typically target AR-signalling, but are rapidly bypassed, resulting in only a modest survival benefit with the anti-androgens.
“Therapeutic approaches that more effectively block AR are urgently needed.
“We demonstrate that CDK7 inhibition selectively targets Med1 and AR, thus representing a potential new approach for the treatment of CRPC.”
