©TheCanadian Journal ofUrology™: International Supplement, April 2014
Addresscorrespondence toDr.ChristopherP.Evans,Deptof
Urology,UniversityofCalifornia,Davis,SchoolofMedicine,
4860YSt., Suite 3500, Sacramento, CA95817USA
The changing landscapeof advanced
and castration resistant prostate cancer:
latest scienceand reviseddefinitions
DeryaTilki,MD,
1,2
Christopher P. Evans,MD
1
1
Department ofUrology,UniversityofCalifornia,Davis,MedicalCenter, Sacramento, California,USA
2
Martini-ClinicProstateCancerCenter,UniversityHospitalHamburg-Eppendorf,Hamburg,Germany
TILKI D, EVANS CP. The changing landscape of
advanced and castration resistant prostate cancer:
latestscienceandreviseddefinitions.
Can JUrol
2014;
21(Suppl 1):7-13.
Introduction:
One fifth of men with newly diagnosed
prostatecancerpresentwith locallyadvancedormetastatic
disease. Androgen deprivation therapy (ADT) is the
standardsystemictherapy inthesepatients. Despite initial
response, essentially all patients will develop castration
resistant prostate cancer (CRPC). In this review,wewill
discuss the revised definitions of CRPC and the latest
understanding of the biology of the androgen/androgen
receptor axis in the development of advanced prostate
cancer.
Materialsandmethods:
Asystematic literature review
wasconductedviaelectronicdatabasearticlesbasedontitle,
abstract,study format,andcontent. Themajorityofselected
articles were published between 1992 and 2013. Older
studieswere included selectively if historically relevant.
Results:
Prostate cancer becomes castration resistant
through numerous pathways, including androgen and
androgenreceptor (AR)dependentmechanismsaswellas
ligandandAR independentpathways. Thereforetheterms
androgen-insensitive and hormone-refractory should be
avoided and replaced by the term castration resistant.
Recentadvances inunderstandingmolecularmechanisms
of castration resistance have led to development of novel
CRPC therapeutics.
Conclusions:
CRPC remains an incurable disease.
Further understanding of the pathways involved in
castration resistancewill set the basis for development of
therapies to increase survival in these patients.
KeyWords:
castrationresistant,hormonerefractory,
prostate cancer, androgen receptor, review
amedianof2 to3years.
3
ADTrelieson thedependence
of prostate cancer cells on androgen-receptor (AR)
signaling.
4
Castrationresistantprostatecancer (CRPC)
representsapressing therapeuticchallenge. Currently
it is believed that AR-mediated pathways remain
active inCRPC. Mechanisms of castration resistance
have been studied extensively in the last decade
and have led to development of new therapeutic
options including abiraterone acetate, an androgen
biosynthesis inhibitor which blocks cytochrome
P450-c17 (CYP17),andenzalutamide,anARsignaling
inhibitor which prevents androgen binding, nuclear
translocation and chromatinbinding.
5-7
Theaimof this review is to summarize the revised
definitions of CRPC and the latest understanding of
the biology of the androgen/androgen receptor axis
in thedevelopment ofCRPC.
Introduction
Despiteearly-detectioneffortsprostatecancerremains
the second-leading cause of cancer-relatedmortality
inmen inWestern societies.
1
One fifth of menwith
newly diagnosed prostate cancer present with
locally advanced or metastatic disease.
2
Androgen
deprivation therapy (ADT) is the standard systemic
therapy in patients with locally advanced prostate
cancer, biochemically recurrent disease after failed
curative treatment and metastatic prostate cancer.
After initial response toADT, thevastmajorityof these
patientswillgoon tocastrationresistantdiseasewithin
7
