title: Therapeutic targeting of the prostate cancer microenvironment.
abstract: Solid tumors can be thought of as multicellular 'organs' that consist of a variety of cells as well as a scaffold of noncellular matrix. Stromal-epithelial crosstalk is integral to prostate cancer progression and metastasis, and androgen signaling is an important component of this crosstalk at both the primary and metastatic sites. Intratumoral production of androgen is an important mechanism of castration resistance and has been the focus of novel therapeutic approaches with promising results. Various other pathways are important for stromal-epithelial crosstalk and represent attractive candidate therapeutic targets. Hedgehog signaling has been associated with tumor progression, growth and survival, while Src family kinases have been implicated in tumor progression and in regulation of cancer cell migration. Fibroblast growth factors and transforming growth factor beta signaling regulate cell proliferation, apoptosis and angiogenesis in the prostate cancer microenvironment. Integrins mediate communication between the cell and the extracellular matrix, enhancing growth, migration, invasion and metastasis of cancer cells. The contribution of stromal-epithelial crosstalk to prostate cancer initiation and progression provides the impetus for combinatorial microenvironment-targeting strategies.
authors.affiliation: Department of Genitourinary Medical Oncology, David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77230-1439, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Karlou
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Tzelepi
authors.forename: Eleni
authors.initials: E
authors.lastname: Efstathiou
mesh_terms: D002986:Clinical Trials as Topic; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D059016:Tumor Microenvironment
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