Investigation of assosiation beetwen megalin exspresion and sonic hedgehog pathway in prostate cancer stem cell

Although advanced prostate cancer initially responds to androgen deprivation therapy (ADT), this initially effective treatment results in an aggressive and often unhealthy condition, and the disease progression to invasive and metastatic curettage-resistant prostate cancer development (mCRPCs) is not yet reversible. Current therapies generally target neoplastic, rapidly growing cancer cells, but in order to be more effective and successful, need to target cancer stem cells (CSC) that consist of few cells within cancer cell populations. CSCs is a group of cells consisting of very few cells in the tumor structure that are resistant to conventional treatments, invasive and even metastatic and ability proliferation endless by itself and keeping silent such as stem cell. The deregulation of the multiple signaling pathways in the stem cells including the Hh, Wnt, Notch and BMP pathways have been related with the formation and expansion of cancer. SHH signaling plays role in transformation of prostate basal ⁄ stem cells into prostate cancer stem cells (PCSCs) and regulates maintance and survival of cancer stem cells. Megalin/LRP2 is the endosytic reseptor that acts as reseptor of SHH and stimulates or suppresses of SHH pathway in contex-depedent–manner in the healthy tissues. To determined megalin role as biologic marker for inhibition of SHH pathway in CSC will provide promising therapeutic target to eliminate CSC, prevent metastasis and invasion and decrease drug resistance. However, more detailed examination of genetic and epigenetic factors that affect megalin expression and function, spesific for prostate CSC and new functional studies fort he megalin-mediated regulation of SHH pathway should be done and the obtained data should be compared with clinical data of prostate cancer patients. In addition, prostate interactions between SHH pathway and and other pathways such as Wnt, Notch and BMP, TGFß pathways should be investigated in prostate CSC.