The genomic and microenvironmental factors affecting neuroendocrine differentiation in prostate cancer induced by androgen deprivation therapy

Although advanced prostate cancer(PCa)can be initially controlled by androgen deprivation therapy(ADT),recurrence normally occurs due to the appearance of castration-resistant prostate cancer(CRPC).Neuroendocrine differentiation(NED)in PCa can be partly explained the androgen resistance and progression to CRPC.NED normally associates with more aggressive clinical behaviour and poor outcomes in PCa.Although more and more studies are performed on NED in PCa recent decades,the molecular profiles that are implicated in NED are still poorly elucidated.Of these studies,signaling factors involved in genomic and microenvironmental components are deeply researched and most likely to provide the potential therapeutic targets for advanced PCa with NED.In this article,we review the hypothesis about the origin of NE cells and the molecular mechanisms driving NED from the point of genomic and environmental views.In addition,we discuss the current potential therapeutic targets and ongoing clinical trails associated with these molecular factors for the treatment of NED patients induced by ADT.

Relationship between tumor lymphangiogenesis and tumor metastasis

Objective:To summarize the research progress on the relationship between tumor lymphangiogenesis and tumor metastasis.Methods:PubMed and China National Knowledge Infrastructure(CNKI)database were used to search for related literatures with the keywords of"tumor,lymphangiogenesis and lymphatic metastasis".Inclusion criteria:(1)the morphology and function of tumor lymphatic vessels;(2)the markers of lymphatic vessels;(3)the mechanism of tumor lymphangiogenesis;(4)the molecular regulation mechanism of tumor lymphangiogenesis.Results:The lymphatic vessel wall is only composed of endothelial cells,and the basement membrane is discontinuous with high permeability.The markers of lymphatic vessels include VEGFR-3,LYVE-1,podoplanin and thehomeoboxgene Prox-1,which facilitate the research on the function of lymphatic vessels in tumor.The mechanism of tumor lymphangiogenesis is very complicated,and there is no conclusion yet.It is believed that the tumor lymphangiogenesis is mainly derived from the existing lymphatic endothelial cells in the tissue.During the process of tumor lymphangiogenesis,many factors,such as VEGF-C,VEGF-D,VEGF-A,bFGF,PDGF-BB,Ang-2,NO and COX-2,are directly or indirectly involved.However,most studies believe that VEGF-C and VEGF-D are the most important regulators of tumor lymphangiogenesis.Conclusion:Tumor lymphangiogenesis is closely related to tumor lymphatic metastasis.Inhibition of tumor lymphangiogenesis can open a new way for tumor treatment.