Drug resistance in certain prostate cancers can be reversed by stopping tumours from “hijacking” a subset of white blood cells in order to help fuel their growth.

This is the conclusion of an international team of researchers who have demonstrated in an early clinical trial that targeting the messages cancer cells use to pull in these white blood cells can benefit one in four patients.

In these cases, by re-sensitising the tumours to treatment, the team were able to go on to either halt tumour growth or even cause them to shrink.

The team trialled their experimental drug, “AZD5069”, in combination with enzalutamide — a hormone therapy commonly used to treat prostate cancer — in patients with an advanced version of the disease.

In a quarter of patients, tumours were seen to shrink by around a third, a feat accompanied by a reduction in blood-based biomarkers of cancer, as well as a reduction in the levels of myeloid cells in both tumours and the bloodstream.

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The body has two main types of white blood cells. Lymphocytes are used to fight viral infections, while myeloid cells fight bacteria and parasites, and prevent the spread of tissue damage.

According to the researchers, myeloid cells are pulled into tumours, at which point they enter a kind-of sleeping state known as “senescence”.

At this point, they become “hormone factories”, pumping out the signals which promote tumour growth, division and survival.

They also send further messages to the bone marrow to recruit even more myeloid cells into tumours, creating a vicious feedback loop.

AZD5069, however, breaks this cycle by blocking the “CXCR2” receptor on myeloid cells, which acts like a “mailbox” for recruitment messages sent by their cancer-co-opted peers.

The study was led by oncologist Professor Johann De Bono of the Institute of Cancer Research (ICR) and the Royal Marsden NHS Foundation Trust.

He said: “This research proves for the first time that targeting myeloid cells rather than the cancer cells themselves can shrink tumours and benefit patients.

“We’ve been studying these myeloid cells at the ICR for many years. More than a decade ago we first noticed that they were elevated in patients with much more aggressive tumours, and showed these tumours were more treatment resistant.

“Professor Andrea Alimonti at the Institute of Oncology Research (IOR) then demonstrated in laboratory studies that these cells could promote prostate cancer growth, with their inhibition blocking tumour progression.”

De Bono continued: “It’s hugely rewarding to see our theory proven in a trial of patients with this disease.

“Myeloid cells may be implicated in treatment resistance in a range of cancers, so the impact of this research could be very broad, across multiple cancer types.

“It’s a major achievement to plan and run a clinical trial on predominantly charity funding.

“We’re incredibly grateful to the charities like Prostate Cancer UK, Cancer Research UK, the Prostate Cancer Foundation and Swiss Card Onco grant organisation, who made this research possible.”

Dr Matthew Hobbs — director of research at Prostate Cancer UK — said: “A man living with advanced prostate cancer needs treatments that will control his disease to give him years more life, feeling as well as possible.

“Sadly, for many men, their cancer resists treatments, ending too many lives far too soon.

“Six years ago, Prostate Cancer UK brought together some of the world’s top experts in the field to work out how prostate cancer is using the immune system to evade treatments, and how we can disrupt this.

“Since then, we’ve moved from initial ideas to laboratory research, and now to a clinical trial that shows us a completely new, safe, effective way treat advanced prostate cancer without resistance.

“I’m extremely excited by these results, and proud that we’re funding such revolutionary research.

“Now we want to see pharmaceutical companies working with researchers to develop new drugs based on what we’ve learnt, and to test them in larger trials — turning research into reality for men.”

The full findings of the study were published in the journal Nature.

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Source: | This article first appeared on Express.co.uk

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