A new treatment re-sensitises advanced prostate cancers to treatment by stopping tumours hijacking myeloid white blood cells to help fuel their growth. The approach has shown benefits for one in four patients and advances scientific understanding of what causes treatment resistance in prostate cancer.
The research demonstrates how prostate cancer’s resistance to treatment can be reversed in some patients by stopping hijacked white blood cells from being ‘pulled into’ tumours. In a trial, researchers showed that blocking the messages cancer uses to hijack white blood cells can re-sensitise a subset of advanced prostate cancers to treatment – shrinking tumours or halting their growth.
The experiments provide the first proof, in a human clinical trial, that targeting ‘feeder’ myeloid white blood cells – which are co-opted by tumours to help fuel cancer growth, progression, and resistance to treatment – can reverse drug resistance and slow tumour progression.
For the trial, the international group of researchers tested a combination of AZD5069, an experimental drug which prevents myeloid cell recruitment to tumours, and the medication enzalutamide, which is a hormone therapy commonly used to treat prostate cancer. The combination was tested out in 48 patients with advanced disease.
The results showed that five of 21 (24 per cent) patients had evidence of their tumours responding to therapy. Here their tumours shrunk by over 30 percent, and the patients saw decreases in circulating levels of prostate specific antigen (PSA), a marker secreted by the prostate which is often elevated by cancer.
Blood levels of myeloid cells also dropped in patients who received treatment, and biopsies following treatment also revealed fewer myeloid cells within their tumours. Myeloid cells within tumours enter a sleep state called ‘senescence’, and become “hormone factories,” manufacturing signals which support tumour growth, division and survival. They then send further signals to the bone marrow to recruit more ‘conspirator’ myeloid cells to enter the tumour and the cycle continues.
In terms of why this new study is important is because it is the first to prove that blocking this pathway has anti-tumour activity in humans with prostate cancer. Furthermore, it is an example of a treatment that works by disrupting the cancer ecosystem.
In terms of specific actions, the treatment AZD5069 prevents myeloid cells being recruited to tumours by blocking a receptor on myeloid cells called CXCR2, which acts as a mailbox for recruitment messages sent by myeloid cells already residing in tumours. These messages encourage myeloid cells to travel towards places of inflammation, such as tumours, and infiltrate them.
The research appears in the science journal Nature, titled “Targeting myeloid chemotaxis to reverse prostate cancer therapy resistance.
