The HOX genes network in uro-genital cancers: mechanisms and potential therapeutic implications

Genito-urinary malignancies (prostate, bladder, renal and testicular cancers) rank high among human tumors with an incidence that varies with age and organ involvement. Prostate cancer is the most commonly detected male cancer followed by bladder and kidney cancers, less frequent in women. Testicular cancer, although rare, is the most frequent cancer in males under 35. The majority of oncogenic and tumor suppressor signaling pathways involved with urogenital cancers converge on sets of transcription factors that ultimately control gene expression resulting in tumor formation and metastatic progression. The activity of these transcription factors is modulated by multiple mechanisms spanning from transcriptional regulation, deregulation of the splicing, maturation, export and location of mRNAs, protein synthesis and post-translational modifications. The recent involvement of the epigenitic mechanisms in the generation and the evolution of cancer has produced a great deal of interest. This is related to the possibility that revealing these mechanisms able to regulate the cell memory program (the gene systems polycomb, trithorax and HOX) may generate important biological and therapeutic achievements. The HOX gene network is the only physically and functionally identifiable transcription factor network located in the human genome controlling crucial cellular processes. Here we describe the implication of the HOX genes in the urogenital embryonic development and cancers. We further highlight the mechanisms uncovered along these processes and involving the HOX genes. Finally, we foresee the specific targeting of HOX genes and in general the cell memory gene program in the therapeutic setting of urogenital malignancies due to their upstream location in these stepwise cell processes and their early deregulation in cancer evolution.