Therapeutic targeting of protein kinase CK2 gene expression in feline oral squamous cell carcinoma - a naturally occurring large animal model of head and neck cancer.

Related Articles

Therapeutic targeting of protein kinase CK2 gene expression in feline oral squamous cell carcinoma - a naturally occurring large animal model of head and neck cancer.

Hum Gene Ther Clin Dev. 2017 Mar 23;:

Authors: Cannon C, Trembley J, Kren B, Unger G, O'Sullivan MG, Cornax I, Modiano J, Ahmed K

Abstract
Protein kinase CK2 (CK2) is a highly promising target for cancer therapy and anti-CK2 gene expression therapy has shown effectiveness in rodent models of human head and neck cancer (HNC). To date, there has been no large animal model of cancer in which to further explore anti-CK2 therapies. Feline oral squamous cell carcinoma (FOSCC) has been proposed as a large animal model for human HNC and we have previously shown that CK2 is a rational target in FOSCC. We hypothesized that a novel tenfibgen coated tumor-specific nanocapsule carrying RNAi oligonucleotides targeting feline CK2α and CK2α' (TBG-RNAi-fCK2αα') would be safe in cats with FOSCC. Assessment of target inhibition and tumor response were secondary aims. 9 cats were enrolled at 2 dose levels in a 3+3 escalation. Cats received a total of six treatments of TBG-RNAi-fCK2αα'. Pre- and post-treatment, tumor and normal oral mucosa biopsies were collected to assess CK2 expression using immunohistochemistry (IHC) preparations evaluated by light microscopy. Toxicity and tumor response were assessed using standard criteria. The most common adverse events were grade 1 or 2 weight loss and anorexia. Grade 3 tissue necrosis was seen associated with tumor response in one cat, asymptomatic grade 4 elevations in AST and CPK in one cat, and asymptomatic grade 3 hypokalemia in one cat. Of 6 cats with evaluable biopsies, 2 had reduction in CK2 IHC scores in tumors following treatment. Four cats had progressive disease during the study period, 3 had stable disease, one had partial response, and response could not be evaluated in one cat. We conclude that the drug appeared safe and there is some evidence of efficacy in FOSCC. Further investigation regarding dosing, schedule, target modulation, toxicity and efficacy in a larger group of cats is warranted and may inform future clinical studies in human head and neck cancer.

PMID: 28335614 [PubMed - as supplied by publisher]

http://ift.tt/2o5fs1N