American Association for Cancer Research
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crc-23-0235-s01.pdf (116.83 kB)

Supplemental Table 1 from AKR1C3 Converts Castrate and Post-Abiraterone DHEA-S into Testosterone to Stimulate Growth of Prostate Cancer Cells via 5-Androstene-3β,17β-Diol

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journal contribution
posted on 2023-09-19, 14:20 authored by Andrea J. Detlefsen, Clementina A. Mesaros, Ling Duan, Trevor M. Penning

Structures of AKR1C3 Inhibitors

Funding

HHS | NIH | National Institute of Environmental Health Sciences (NIEHS)

HHS | NIH | National Institute of General Medical Sciences (NIGMS)

History

ARTICLE ABSTRACT

We show that reservoirs of DHEA-S that remain after ARSI treatment are converted into T in primary and metastatic prostate cancer cells in amounts sufficient to stimulate cell growth. Pharmacologic and genetic approaches demonstrate that AKR1C3 is required for these effects. Furthermore, the route to T proceeds through 5-Adiol. We propose that this is a mechanism of ARSI drug resistance.