Title:Molecular Foundations for Personalized Therapy in Prostate Cancer
Volume: 16
Issue: 2
Author(s): Kurt W. Fisher, Rodolfo Montironi, Antonio Lopez Beltran, Holger Moch, Lisha Wang, Marina Scarpelli, Sean R. Williamson, Michael O. Koch and Liang Cheng
Affiliation:
关键词:
雄激素受体、分子细胞遗传学、神经内分泌/小细胞癌，个体化医学、前列腺癌、靶向治疗，TMPRSS2-ERG重排
摘要: Prostate cancer is the most common and second most lethal cancer in men. The majority of prostate cancers
are histologically similar to acinar adenocarcinomas and rely on androgen-dependent signaling for their development
and progression. Androgen deprivation therapy is a mainstay of treatment regimens and we discuss the recent advancements
in androgen-deprivation therapy. Recent advances in defining the genetic landscape of prostate cancer
have shown that the depth of genetic heterogeneity surpasses what can be seen histologically and has the ability to redefine
treatments. TMPRSS2–ETS family fusion proteins are unique to prostate cancer and we discuss their role in
carcinogenesis, prognosis, and the development of TMPRSS2–ETS family gene fusion targeted therapy. Inactivation
of the tumor suppressor PTEN leads to activation of the PI3K/Akt/mTOR pathway and we discuss the prognostic and
treatment implications. Molecular genetic analysis has recently demonstrated that clinically aggressive high grade neuroendocrine
prostate carcinomas contain a high prevalence of overexpression of Aurora A kinase and N-myc. We discuss
the role of Aurora A kinase and N-myc in the development of the aggressive neuroendocrine phenotype and the
development of targeted inhibitors of this specific genetic subtype. Lastly, we briefly discuss emerging genetic subtypes
defined by either SPINK1 overexpression, CHD1 inactivation, or SPOP mutations. By reviewing the associations
between the morphologic features and the molecular genetics of prostate cancer we hope to provide insight and guidance
to the emerging options for targeted therapy.
