Journal of Pharmacovigilance

The cyclic GMP/protein kinase G pathway as a therapeutic target in head and neck squamous cell carcinoma

Conference Series LLC Joint International Event on 7^th Pharmacovigilance & Pharmaceutical Industry

August 22-24, 2016 Vienna, Austria

Nira Ben-Jonathan

University of Cincinnati, USA

Posters & Accepted Abstracts: J Pharmacovigil

Abstract:

Head and neck squamous cell carcinoma (HNSCC) is an aggressive disease with high mortality. Treatments, which can result in significant morbidity and decreased quality of life, have not substantially changed in the last three decades. We are introducing the cGMP/protein kinase G (PKG) axis as an intrinsic apoptotic pathway which is inactive in many HNSCC cell lines. The second messenger cGMP is generated by guanylate cyclases (GCs), and is rapidly hydrolyzed by phosphodiesterases (PDEs). Activation of the cGMP/PKG pathway is antineoplastic in several cancer types, but its impact on HNSCC has not been previously exploited. We found differential expression of critical components of this pathway in four HNSCC cell lines. Activators of soluble GC (sGC) as well as inhibitors of PDE5 (which degrades cGMP), increased intracellular cGMP, reduced cell viability, induced apoptosis, and increased chemo-and radio-sensitivity in HNSCC cells. Apoptosis by the sGC activator BAY 41-2272 and the PDE5 inhibitor Tadalafil (Cialis) were mediated by PKG. Cialis substantially reduced the growth of CAL27-derived xenografts in athymic mice. Several drugs which activate sGC or inhibit PDE5 are approved for treatment of nonmalignant conditions. These drugs could be repurposed as novel and effective therapeutics in patients with head and neck cancer.

Biography :

Email: BENJONN@UCMAIL.UC.EDU