Journal
CURRENT ONCOLOGY REPORTS
Volume 20, Issue 8, Pages -Publisher
SPRINGER
DOI: 10.1007/s11912-018-0707-9
Keywords
Androgen receptor; Androgen deprivation therapy; Genomics; SPOP; CHD1; ETS; ERG; SPINK1; PTEN; TP53; NEPC; CRPC; HG-PIN; FOXA1; Rearrangements; Prognosis; Metastasis; Clonal; Subclonal; TMPRSS2; Taxonomy; PARP; IDH1; BRCA2; ATM
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Funding
- US NCI [K08CA187417-01, P50CA211024-01, R01CA215040-01]
- Urology Care Foundation Rising Star in Urology Research Award
- Damon Runyon Cancer Research Foundation MetLife Foundation Family Clinical Investigator Award
- Prostate Cancer Foundation
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This review will examine the taxonomy of PCa subclasses across disease states, explore the relationship among specific alterations, and highlight current clinical relevance. 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. 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.
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