GENITOURINARY CANCERS (DP PETRYLAK AND JW KIM, SECTION EDITORS)
Molecular Subtypes of Prostate Cancer
Christopher E. Barbieri
Springer Science+Business Media, LLC, part of Springer Nature 2018
Purpose of Review This review will examine the taxonomy of PCa subclasses across disease states, explore the relationship
among specific alterations, and highlight current clinical relevance.
Recent Findings Prostate cancer (PCa) is driven by multiple genomic alterations, with distinct patterns and clinical implications.
Alterations occurring early in the timeline of the disease define core subtypes of localized, treatment-naive PCa. With time, an
increase in number and severity of genomic alterations adds molecular complexity and is associated with progression to
metastasis. These later events are not random and are influenced by the underlying subclasses.
Summary All the subclasses of localized disease initially respond to androgen deprivation therapy (ADT), but with progression
to castrate-resistant PCa (CRPC), mechanisms of resistance against ADT shift the molecular landscape. In CRPC, resistance
mechanisms largely define the biology and sub-classification of these cancers, while clinical relevance and opportunities for
precision therapy are still being defined.
Keywords Androgen receptor
Androgen deprivation therapy
Prostate cancer (PCa) is the third leading cause of cancer death
in men with an estimate of 29,430 deaths in 2018 .
Prevalence of prostate cancer highly depends on age, family
history, race, and genetic susceptibility . The natural history
of PCa is long and is believed to extend over decades. Prostate
neoplasia is thought to originate with a premalignant lesion
known as high grade prostatic intraepithelial neoplasia (HG-
PIN). HG-PIN is characterized by the presence of abnormal
cytologic features of epithelial cells in the glands or ducts of
the prostate . HG-PIN shares various morphological and
genomic features with PCa and has been suggested as a tran-
sition phase between benign prostate epithelium and invasive
cancer . This transition phase embarks with localized PCa,
as a disease stage.
Localized PCa is an early stage of malignancy that is con-
fined to the prostate and is often categorized as either indolent
or aggressive based largely on clinical and pathological fea-
tures (e.g., Gleason score, PSA levels). Treatment options
available at this stage of PCa include surgery, radiation thera-
py, and less often, androgen deprivation therapy (ADT).
Nonetheless, PCa reoccurs in up to 35% of cases and pro-
gresses to metastasis where it spreads to bones, lymph nodes,
and bladder [4–6]. This stage of PCa is still sensitive to ADT
and is, therefore, called metastatic hormone sensitive prostate
cancer (HSPC). ADTis commonly used in prostate cancer due
to its dependence on androgen receptor (AR) signaling.
AR belongs to a nuclear hormone receptor family of tran-
scription factors . After binding to its ligand (testosterone
and other androgens), AR binds to promoter region of its
This article is part of the Topical Collection on Genitourinary Cancers
* Christopher E. Barbieri
Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine,
Belfer Research Building, BRB 1452, 413 East 69th Street, New
York, NY 10021, USA
Department of Urology, Weill Cornell Medicine, New York, NY,
Englander Institute for Precision Medicine of Weill Cornell Medicine
and NewYork-Presbyterian Hospital, New York, NY, USA
Current Oncology Reports (2018) 20:58