Continued androgen signalling inhibition improves cabazitaxel efficacy in prostate cancer

Mout, Lisanne; Royen, Martin E. van; Ridder, Corrina de; Stuurman, Debra; Geer, Wesley S van de; Marques, Rute B.; Buck, Stefan A.J.; French, Pim J.; Werken, Harmen J.G. van de; Mathijssen, Ron H.J.; Wit, Ronald de; Lolkema, Martijn P.; Weerden, Wytske M. van

doi:10.1016/j.ebiom.2021.103681

Cited by 8 publications

(1 citation statement)

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“…The androgen receptor pathway is a key driver of prostate cancer progression [27]. Androgen activates the androgen receptor which is critical for survival and proliferation of androgen-sensitive prostate cancer cells [28].…”

Section: Androgens Drive Prostate Cancer Cells Into Mitosismentioning

confidence: 99%

Androgen Flare after LHRH Initiation Is the Side Effect That Makes Most of the Beneficial Effect When It Coincides with Radiation Therapy for Prostate Cancer

Nasser

2022

Cancers

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Treatment of metastatic prostate cancer was historically performed via bilateral orchiectomy to achieve castration. An alternative to surgical castration is the administration of subcutaneous recombinant luteinizing hormone-releasing hormone (LHRH). LHRH causes the pituitary gland to produce luteinizing hormone (LH), which results in synthesis and secretion of testosterone from the testicles. When LHRH levels are continuously high, the pituitary gland stops producing LH, which results in reduced testosterone production by the testicles. Long-acting formulations of LHRH were developed, and its use replaced surgical orchiectomy in the vast majority of patients. Combining LHRH and radiation therapy was shown to increase survival of prostate cancer patients with locally advanced disease. Here, we present a hypothesis, and preliminary evidence based on previous randomized controlled trials, that androgen surge during radiation, rather than its suppression, could be responsible for the enhanced prostate cancer cell kill during radiation. Starting LHRH agonist on the first day of radiation therapy, as in the EORTC 22863 study, should be the standard of care when treating locally advanced prostate cancer. We are developing formulations of short-acting LHRH agonists that induce androgen flare, without subsequent androgen deprivation, which could open the door for an era in which prostate cancer could be cured while patients maintain potency.

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Section: Androgens Drive Prostate Cancer Cells Into Mitosismentioning

confidence: 99%