Abstract
Prostate cancer is the second most frequently diagnosed cancer in men and several therapeutic approaches are currently available for patient’s care. Although the androgen receptor status represents a good predictor of response to androgen deprivation therapy, prostate cancer frequently becomes resistant to this approach and spreads. The molecular mechanisms that contribute to progression and drug-resistance of this cancer remain still debated. However, few therapeutic options are available for patient’s management, at this stage. Recent years have seen a great expansion of the studies concerning the role of stromal-epithelial interactions and tumor microenvironment in prostate cancer progression. The findings so far collected have provided new insights into diagnostic and clinical management of prostate cancer patients. Further, new fascinating aspects concerning the intersection of the androgen receptor with survival factors as well as calcium channels have been reported in cultured prostate cancer cells and mouse models. The results of these researches have opened the way for a better understanding of the basic mechanisms involved in prostate cancer invasion and drug-resistance. They have also significantly expanded the list of new biomarkers and druggable targets in prostate cancer. The primary aim of this manuscript is to provide an update of these issues, together with their translational aspects. Exploiting the power of novel promising therapeutics would increase the success rate in the diagnostic path and clinical management of patients with advanced disease.
Highlights
Prostate cancer (PC) still remains the second most commonly diagnosed neoplasia in men [1]
The action of neurotrophins is mediated by the binding to membrane receptors, mainly the neurotrophin receptor p75NTR and the neurotrophin tyrosine kinase receptor (Trk) family, which consists of three members, tropomyosin-related kinase receptor A (TrkA), B and C, with a variable affinity for the four identified neurotrophins (NGF; brainderived neurotrophic factor, brain-derived neurotrophic factor (BDNF); neurotrophin 3 and 4, NT3 and NT4; Figure 1)
The proposed findings identify the NRG1/Receptor tyrosine-protein kinase erbB-3 (HER3) axis as a main candidate in the antiandrogen resistance. In support of this concept, high levels of NRG1, together with an enhanced NRG1 mRNA expression, can be detected in cancer associated fibroblast (CAF) from androgen deprivation therapy (ADT)-treated PC patients [17]. These results suggest that targeting of the NRG1/HER3 axis may be beneficial in castrate-resistant prostate cancer (CRPC) patients
Summary
Fabrizio Licitra , Pia Giovannelli , Marzia Di Donato , Alessandra Monaco , Giovanni Galasso , Antimo Migliaccio* and Gabriella Castoria*. The androgen receptor status represents a good predictor of response to androgen deprivation therapy, prostate cancer frequently becomes resistant to this approach and spreads. The findings so far collected have provided new insights into diagnostic and clinical management of prostate cancer patients. New fascinating aspects concerning the intersection of the androgen receptor with survival factors as well as calcium channels have been reported in cultured prostate cancer cells and mouse models. The results of these researches have opened the way for a better understanding of the basic mechanisms involved in prostate cancer invasion and drugresistance.
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