Seminar: Radiosensitivity of Prostate Cancer Cells Treated with Estrogen Therapy and Androgen-Deprivation Therapy

Student: Catherine Mckenna

Supervisor: Dr. Eric Da Silva

Abstract

Transgender women receiving gender-affirming care are at risk for developing prostate cancer, as gender-affirming surgery (GAS) keeps the prostate intact. Gender-affirming hormone therapy (GAHT), such as combined androgen deprivation therapy (ADT) with estrogen therapy (ET), may be used to induce
feminization. Similar hormone therapy is used to treat prostate cancer in cisgender men by inducing castrate levels of androgen to halt disease progression. Prostate cancer which progresses despite ADT is referred to as castration-resistant or androgen-independent, and is associated with worse prognosis. Therefore, prostate cancer in transgender women receiving long-term GAHT tends to be castration-resistant, late stage, and metastatic, upon diagnosis. Transgender women are a significantly understudied population and there is currently no standard treatment practice defined, though most cases have been treated with radiotherapy or radical prostatectomy. The effects of GAHT on prostate cancer radiotherapy remain poorly understood; thus, this research aims to investigate the radiosensitivity of castration-resistant prostate cancer treated with ET and ADT.

Proposed methods to investigate the effects of ET and ADT on the radiosensitivity of prostate cancer include in vitro studies with androgen-dependent (LNCaP) and androgen-independent (PC3) prostate cancer cell lines. Cells will be incubated with varying hormone conditions to simulate ET + ADT (estradiol, testosterone, and androgen-receptor inhibitors), no hormone suppression (testosterone and estradiol), and surgical castration with ET (estradiol). Cells will then be exposed to a range of X-ray doses to measure and compare the impact on cell survival via clonogenic assay. Other measures to consider include quantifying DNA damage by immunofluorescence or comet assay, and radiation-induced apoptosis by flow cytometry. This study aims to provide insight into how GAHT influences the response to radiotherapy, potentially informing future treatment strategies for transgender women with prostate cancer.