Introduction

Feline pulmonary carcinomas are uncommon tumors and pet cats are often diagnosed with late-stage disease which is unamenable to curative surgical resection and clinically analogous to the dilemma encountered in people diagnosed with NSCLC. NQO1 is a detoxifying enzyme overexpressed in many human solid tumors and serves as a druggable target given its preferential expression by tumor cells. Isobutyl-deoxynyboquinone (IB-DNQ) is a specific substrate for NQO1, resulting in reactive oxygen species (ROS) generation and cell death. We have generated data identifying NQO1 overexpression in several feline and canine solid tumors, and have demonstrated the anti-cancer activity of IB-DNQ in pet cats with unresectable oral squamous cell carcinoma. To extend upon these promising findings, we hypothesize that NQO1 will also be overexpressed by feline pulmonary carcinomas and will serve as a druggable target of IB-DNQ.

Methods

Fifty-one archived feline pulmonary carcinomas were assessed for NQO1 expression by immunohistochemical (IHC) methods. NQO1 protein expressions (Western blot and IHC) and enzymatic activities were characterized in pulmonary carcinoma cell lines derived from 3 species (human, feline, murine) and cytotoxic activities of IB-DNQ correlated with relative NQO1 expressions.

Results

The vast majority of feline pulmonary carcinomas (50/51, 98%) express NQO1 protein. All cell lines expressed NQO1 protein and enzymatic activities. IB-DNQ at biologically-achievable concentrations exerts cytotoxicity against all cell lines and on-target specificity (EC50s correlated with NQO1 expression and activity).

Conclusion

NQO1 is robustly expressed by feline pulmonary carcinomas and IB-DNQ warrants clinical evaluation in pet cats diagnosed with pulmonary carcinomas as a rational and targeted treatment option.