title: Kallikrein-related peptidases targeted therapies in prostate cancer: perspectives and challenges.
abstract: BACKGROUND
  Despite the emergence of several new effective treatments for metastatic castration-resistant prostate cancer patients, disease progression inevitably occurs, leading scientific community to carefully look for novel therapeutic targets of prostate cancer. Kallikrein (KLK)-related peptidases have been demonstrated to facilitate prostate tumorigenesis and disease progression through the development of an oncogenic microenvironment for prostate cells.
  
  
  METHODS
  This review first summarizes the large amount of preclinical data showing the involvement of KLKs in prostate cancer pathobiology. In the second part, the authors assess the current status and future directions for KLK-targeted therapy and briefly describe the advances and challenges implicated in the design of effective manufactured drugs. The authors then focus on the preclinical data and on Phase I/II studies of the most promising KLK-targeted agents in prostate cancer. The drugs discussed here are divided on the basis of their mechanism of action: KLK-engineered inhibitors; KLK-activated pro-drugs; KLK-targeted microRNAs and small interfering RNAs(-/)small hairpin RNAs; KLK vaccines and antibodies.
  
  
  CONCLUSIONS
  Targeting KLK expression and/or activity could be a promising direction in prostate cancer treatment. Future human clinical trials will help us to evaluate the real benefits, toxicities and the consequent optimal use of KLK-targeted drugs, as mono-therapy or in combination regimens.
authors: 1 University of Rome Tor Vergata, Tor Vergata University Clinical Center, Department of Systems Medicine, Medical Oncology , Viale Oxford 81, 00133 Rome , Italy +39 0620908190 ; +39 0620903504 ; vittore.cereda@gmail.com.
authors: Vittore
authors: V
authors: Cereda
authors: Vincenzo
authors: V
authors: Formica
authors: Antonello
authors: A
authors: Menghi
authors: Stefania
authors: S
authors: Pellicori
authors: Mario
authors: M
authors: Roselli
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007610:Kallikreins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D007610:Kallikreins
keywords: engineered inhibitors; immunotherapy; kallikrein; kallikrein-activated prodrugs; kallikrein-targeted therapy; prostate cancer