Scientists discover way to reverse drug resistance in prostate cancer

2023-10-19

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Scientists discover way to reverse drug resistance in prostate cancer

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来源: PMLiVE

Researchers from the Institute of Cancer Research (ICR)Cancer Research (ICR), the Royal Marsden NHS Foundation Trust and the Institute of Oncology Research (IOR) have discovered a way to reverse drug resistance in prostate cancer.

In an early clinical trial, the researchers found that stopping ‘hijacked’ white blood cells from being pulled into tumours can reverse drug resistance and slow tumour progression.

The study, part funded by Prostate Cancer UK, Cancer Research UK, the ICR and AstraZeneca, as well as others, tested a combination of AZD5069, an experimental drug to prevent myeloid cell recruitment to tumours, and enzalutamide, a commonly used hormone therapy to treat prostate cancer, in patients with advanced disease.

AZD5069 works by blocking a receptor called CXCR2, located in myeloid cells, which sends messages from myeloid cells to existing tumours.

Myeloid white blood cells can be co-opted by tumours to progress cancer growth, progression and resistance to treatment.

The researchers found that 24% of the patients responded well to the treatment, meaning their tumours shrunk by over 30%, they saw dramatic decreases in circulating levels of prostate specific antigen, a marker secreted by the prostate which is often elevated by cancer, or their blood levels of circulating tumour cells dropped.

Additionally, blood levels of myeloid cells decreased in patients who received the treatment and biopsies revealed fewer myeloid cells within their tumours.

The team have since found that myeloid cells with tumours enter senescence, a sleep state, and become ‘hormone factories’, which produce signals to support tumour growth, division and survival.

The study offers the first proof in a trial of targeting the myeloid white blood cells and blocking the pathway between them to have anti-tumour activity in prostate cancer patients.

Study leader Johann De Bono, professor in experimental cancer medicine at the ICR and consultant medical oncologist at the Royal Marsden NHS Foundation, said: "This research proves for the first time that targeting myeloid cells rather than the cancer cells themselves can shrink tumours and benefit patients.”

Professor Kristian Helin, chief executive officer at the ICR, hopes that this “innovative approach” will “pave the way to a new treatment that is beneficial to people with prostate cancer and potentially also many other cancer types”.

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