Prostate cancer heterogeneity: Discovering novel molecular targets for therapy

•Prostate cancer (PCa) shows a broad spectrum of biological and clinical behavior, which represents the epiphenomenon of an extreme genetic heterogeneity.•The AR and PI3K/Akt/mTOR signaling pathways are the two most frequently altered, representing therefore interestingly targets for therapy.•Germli...

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Published in:Cancer treatment reviews Vol. 54; pp. 68 - 73
Main Authors: Ciccarese, Chiara, Massari, Francesco, Iacovelli, Roberto, Fiorentino, Michelangelo, Montironi, Rodolfo, Di Nunno, Vincenzo, Giunchi, Francesca, Brunelli, Matteo, Tortora, Giampaolo
Format: Journal Article
Language:English
Published: Netherlands Elsevier Ltd 01.03.2017
Subjects:
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
BRCA
CRPC
DNA Repair - drug effects
DNA Repair - genetics
DRG
Hematology, Oncology and Palliative Medicine
Heterogeneity
Humans
Male
Molecular Targeted Therapy - methods
PARPi
Phosphatidylinositol 3-Kinases - metabolism
Prostate cancer
Prostatic Neoplasms - drug therapy
Prostatic Neoplasms - genetics
Prostatic Neoplasms - metabolism
Proto-Oncogene Proteins c-akt - metabolism
PTEN
PTEN Phosphohydrolase - genetics
Receptors, Androgen - metabolism
Signal Transduction - drug effects
TOR Serine-Threonine Kinases - metabolism
Heterogeneity
BRCA
DRG
PTEN
PARPi
Prostate cancer
CRPC
ISSN:0305-7372, 1532-1967, 1532-1967
Online Access:Get full text
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Summary:•Prostate cancer (PCa) shows a broad spectrum of biological and clinical behavior, which represents the epiphenomenon of an extreme genetic heterogeneity.•The AR and PI3K/Akt/mTOR signaling pathways are the two most frequently altered, representing therefore interestingly targets for therapy.•Germline mutations in DNA repair genes (BRCA2, BRCA1, MSH2, HOXB13) have been related to an increased risk of developing PCa.•The PI3K/Akt pathway is the second most commonly genomic aberration hyperactivated in advanced PCa, after AR alterations. Prostate cancer (PCa) shows a broad spectrum of biological and clinical behavior, which represents the epiphenomenon of an extreme genetic heterogeneity. Recent genomic profiling studies have deeply improved the knowledge of the genomic landscape of localized and metastatic PCa. The AR and PI3K/Akt/mTOR signaling pathways are the two most frequently altered, representing therefore interestingly targets for therapy. Moreover, somatic or germline aberrations of DNA repair genes (DRGs) have been observed at high frequency, supporting the potential role of platinum derivatives and PARP inhibitors as effective therapeutic strategies. In the future, the identification of driver mutations present at a specific stage of the disease, the classification PCa based on specific molecular alterations, and the selection of the most appropriate therapy based on biomarkers predictors of response represent the foundations for an increasingly more accurate personalized medicine.
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ISSN:0305-7372
1532-1967
1532-1967
DOI:10.1016/j.ctrv.2017.02.001