Prostate Cancer Hijacks Tumor Cells’ Circadian Rhythm to Evade Hormone Therapy
upstart writes:
Prostate Cancer Hijacks Tumor Cells' Circadian Rhythm To Evade Hormone Therapy:
Hormone treatment is successful at controlling metastatic prostate cancer, but the tumor cells eventually develop resistance to it. An unexpected potential solution has now emerged in medicines that are not designed to fight cancer, but rather to target proteins that regulate a cell's circadian rhythm.
[...] Prostate cancer is a form of tumor that develops under the influence of hormones, primarily testosterone. Patients with metastatic prostate cancer are frequently treated with anti-hormonal therapy, which inhibits the signal sent out by testosterone that stimulates tumor growth.
Anti-hormonal therapy can keep prostate cancer under control for a time, but eventually, the cancer manages to progress despite ongoing treatment. The tumor cells have become resistant. This means that the greatest challenge in treating metastatic prostate cancer isn't to find drugs that inhibit tumor growth itself, but to find drugs that can prevent resistance to hormonal therapy. The exact process of how tumor cells become resistant to hormone therapy, however, has been a mystery - until now.
An international team of researchers led by scientists from the Netherlands Cancer Institute and Oncode Institute has made a surprising discovery using tissue from patients with prostate cancer who had been treated with testosterone-inhibiting drugs. They found that an unexpected class of proteins, namely proteins that normally regulate the circadian clock, dampens the effects of the anti-hormonal therapy. "Prostate cancer cells no longer have a circadian rhythm," says Wilbert Zwart, one of the research leaders. "But these 'circadian clock' proteins acquire an entirely new function in the tumor cells upon hormonal therapy: they keep these cancer cells alive, despite treatment. This has never been seen before."'Drug repurposing could save a decade or research'
Now that they have discovered the tumor's escape route, the researchers will next work together with Oncode towards the development of novel strategies to block this process, and ultimately increase the efficacy of anti-hormonal therapy against prostate cancer even further.
Reference: 27 June 2022, Cancer Discovery.
DOI: 10.1158/2159-8290.CD-21-0576
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