Editing Hormonal Therapy (section)

== Androgen Receptor (AR) and Castrate-Resistant Prostate Cancer (CRPC) ==

* The AR is a ligand-inducible transcription factor, meaning that they cause transcription of target genes within specific cells after ligands (e.g., testosterone) bind to them
* '''Molecular mechanisms implicated in the process of castration resistance (5):'''
*# '''Hypersensitivity:''' the AR pathway can become hypersensitive through a variety of molecular alterations (such as gene amplification) and be activated by even lower levels of androgen
*# '''Promiscuity:''' the AR can be '''activated by ligands other than androgen'''
*# '''Outlaw:''' '''growth factor peptides''' such as epidermal growth factor and insulin-like growth factor-1 '''increase AR transcriptional activity in the absence of androgen'''
*# '''Bypass: activation of parallel or alternative survival pathways''' allows otherwise androgen-dependent prostate cancer cells to survive in the absence of androgen
*# '''Lurker cell: a small population of possible epithelial stem cells is pre-existent in the prostate''' and androgen deprivation selects for the outgrowth of these castration-resistant cells.
* '''ADT should continue in CRPC'''
** '''Even when prostate cancer progresses despite castrate levels of androgen i.e. CRPC, it is rarely resistant to androgen action'''
*** Exogenous androgen results in symptomatic tumor flare in 87% of patients with CRPC
*** '''Although the term hormone-refractory prostate cancer has been widely used''' to describe a state of progressive disease despite ADT, '''the term castration-resistant prostate cancer is more clinically precise and relevant'''