Investigational therapies targeting signal transducer and activator of transcription 3 for the treatment of cancer.
BACKGROUND
Signal transducer and activator of transcription 3 (STAT3) mediates the expression of a variety of genes in response to cell stimuli and thus plays a key role in several cellular processes such as cell growth and apoptosis. Deregulation of the STAT3 activity has been shown in many malignancies, including breast, head and neck, prostate, pancreas, ovarian and brain cancers and melanoma. Thus, STAT3 may represent an ideal target for cancer therapy.


METHODS
The authors review recent data on the role of STAT3 in tumor initiation and progression, as well as the ongoing clinical trials in cancer patients. The content includes information derived from trial databases, regulatory authorities and scientific literature.


CONCLUSIONS
Targeting STAT3 activation leads to the inhibition of tumor growth and metastasis both in vitro and in vivo without affecting normal cells; this suggests that STAT3 could be a valid molecular target for cancer therapy. Extensive clinical research is trying to find anti-STAT3 agents with high single-agent activity. The identification and development of novel drugs that can target deregulated STAT3 activation effectively is both a scientific and clinical challenge that needs to be addressed in the near future.
Polytechnic University of the Marche Region, Medical Oncology, AOU Ospedali Riuniti , via Conca 71, 60126 Ancona , Italy +39 0715964263 ; +39 0715964269 ; mattymo@alice.it.
Matteo
M
Santoni
Francesco
F
Massari
Marzia
M
Del Re
Chiara
C
Ciccarese
Francesco
F
Piva
Giovanni
G
Principato
Rodolfo
R
Montironi
Daniele
D
Santini
Romano
R
Danesi
Giampaolo
G
Tortora
Stefano
S
Cascinu
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000187:drug effects* / Q000378:metabolism
D000970:Antineoplastic Agents; D050796:STAT3 Transcription Factor
cancer; clinical trial; signal transducer and activator of transcription 3; tumor microenvironment