Abstract
Prostate cancer (PCa) represents the most commonly non-cutaneous diagnosed cancer in men worldwide and occupies a very wide area of preclinical and clinical research. Targeted therapy for any cancer depends on the understanding of the molecular bases and natural behaviour of the diseases. Despite the well-known effect of androgen deprivation on PCa, many patients develop resistance either for antiandrogen therapy or other new treatment modalities such as checkpoint inhibitors and chemotherapy. Comprehensive understanding of the development of PCa as well as of the mechanisms underlying its progression is mandatory to maximise the benefit of the current approved medications or to guide the future research for targeted therapy of PCa. The aim of this review was to provide updates on the most recent mechanisms regarding the development and the progression of PCa. According to the current understanding, future treatment strategies should include more predictive genetic and biomarker analysis to assign different patients to the expected most appropriate and effective treatment.
Highlights
Prostate cancer (PCa) represents the most common cancer among men after cutaneous melanoma, occupying the second place with regard to male cancer mortality worldwide [1].In United States, more than 170,000 new cases are diagnosed every year due to PCa, while more than 31,000 people die because of this aggressive type of cancer [2]
Different in vitro and in vivo preclinical studies have highlighted the role played by Insulin-like Growth Factor (IGF) system in the development of PCa, but despite the promising data, most of the clinical studies failed to demonstrate a direct link between the activity of the members of IGF family and the progression of PCa [19]
A recent comprehensive systematic review and meta-analysis suggested a link between milk ingestion and PCa through the modulation of IGFs [20]. Another clinical study linked the prognosis of PCa to the overexpression of IGFR-1 receptor in transmembrane serine protease 2-erythroblast transformation-specific-related gene (TMPRSS2-ERG) (T2E) gene-negative subgroup of patients [21]
Summary
Prostate cancer (PCa) represents the most common cancer among men after cutaneous melanoma, occupying the second place with regard to male cancer mortality worldwide [1]. Despite the effective suppression of androgen signals, many PCa patients will eventually transform into castration-resistant PCa (CRPC), which is characterised by a high rate of metastatic disease (mCRPC) and a poor prognosis. It causes symptoms and, in the worst case scenario, death among PCa patients [6]. Both chemotherapy and immunotherapy have been given an evolving role in the management of PCa. docetaxel chemotherapy administered to patients with mCRPC has represented the standard therapy since 2004, with a minimal survival benefit [7]. Shedding more light on the molecular pathways driving the genesis and progression of PCa is critical for the identification of potential therapy targets as well as to decrease the mortality of this disease
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