Minireview: SLCO and ABC transporters: a role for steroid transport in prostate cancer progression.
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Cho E, Montgomery RB, Mostaghel EA
Minireview: SLCO and ABC transporters: a role for steroid transport in prostate cancer progression.
Endocrinology. 2014 Nov;155(11):4124-32. doi: 10.1210/en.2014-1337. Epub 2014 Aug 22.
- PubMed ID
- 25147980 [ View in PubMed]
- Abstract
Androgens play a critical role in the development and progression of prostate cancer (PCa), and androgen deprivation therapy via surgical or medical castration is front-line therapy for patients with advanced PCa. However, intratumoral testosterone levels are elevated in metastases from patients with castration-resistant disease, and residual intratumoral androgens have been implicated in mediating ligand-dependent mechanisms of androgen receptor activation. The source of residual tissue androgens present despite castration has not been fully elucidated, but proposed mechanisms include uptake and conversion of adrenal androgens, such as dehdroepiandrosterone to testosterone and dihydrotestosterone, or de novo androgen synthesis from cholesterol or progesterone precursors. In this minireview, we discuss the emerging evidence that suggests a role for specific transporters in mediating transport of steroids into or out of prostate cells, thereby influencing intratumoral androgen levels and PCa development and progression. We focus on the solute carrier and ATP binding cassette gene families, which have the most published data for a role in PCa-related steroid transport, and review the potential impact of genetic variation on steroid transport activity and PCa outcomes. Continued assessment of transport activity in PCa models and human tumor tissue is needed to better delineate the different roles these transporters play in physiologic and neoplastic settings, and in order to determine whether targeting the uptake of steroid substrates by specific transporters may be a clinically feasible therapeutic strategy.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Prasterone ATP-binding cassette sub-family G member 2 Protein Humans UnknownSubstrateDetails Prasterone Multidrug resistance-associated protein 1 Protein Humans UnknownSubstrateDetails Prasterone Multidrug resistance-associated protein 4 Protein Humans UnknownSubstrateDetails Prasterone Solute carrier organic anion transporter family member 1A2 Protein Humans UnknownSubstrateDetails Prasterone Solute carrier organic anion transporter family member 1B1 Protein Humans UnknownSubstrateDetails Prasterone Solute carrier organic anion transporter family member 1B3 Protein Humans UnknownSubstrateDetails Prasterone Solute carrier organic anion transporter family member 2B1 Protein Humans UnknownSubstrateDetails Testosterone Solute carrier organic anion transporter family member 1B3 Protein Humans UnknownSubstrateDetails