Conflict of interest: none declared.
Experimental Dermatology ● Concise Report
Increasing the therapeutic efficacy of docetaxel for cutaneous squamous cell carcinoma through the combined inhibition of phosphatidylinositol 3-kinase/AKT signalling and autophagy
Article first published online: 27 MAR 2013
© The Author(s) CED © 2013 British Association of Dermatologists
Clinical and Experimental Dermatology
Volume 38, Issue 4, pages 421–423, June 2013
How to Cite
Wright, T. J., McKee, C., Birch-Machin, M. A., Ellis, R., Armstrong, J. L. and Lovat, P. E. (2013), Increasing the therapeutic efficacy of docetaxel for cutaneous squamous cell carcinoma through the combined inhibition of phosphatidylinositol 3-kinase/AKT signalling and autophagy. Clinical and Experimental Dermatology, 38: 421–423. doi: 10.1111/ced.12138
The first two authors contributed equally to this work, and should be considered joint first authors. The last two authors are joint senior authors.
- Issue published online: 23 APR 2013
- Article first published online: 27 MAR 2013
- Manuscript Accepted: 15 JAN 2013
- The North-eastern Skin Research Fund
- Newcastle Healthcare Charity
- British Skin Foundation
Early-stage cutaneous squamous cell carcinoma (cSCC) has a favourable prognosis. Metastatic disease is probably associated with chemoresistance mediated through the activation of pro-survival phosphatidylinositol 3-kinase/AKT signalling. Inhibition of activated AKT partially increases chemosensitivity but induces autophagy, the principal lysosomal mechanism for the bulk degradation and recycling of proteins and damaged organelles. The aim of the current study was to test the hypothesis that combined inhibition of AKT signalling and autophagy by the lysosomal inhibitor chloroquine increases the susceptibility to docetaxel-induced apoptosis of cSCC cells isolated from a lymph-node metastasis. Combined AKT inhibition and chloroquine treatment of MET 4 cSCC cells resulted in significantly enhanced inhibition of cell viability and apoptosis induced by clinically achievable concentrations of docetaxel (P < 0.001). Inhibition of both autophagy and AKT thus represents an effective and viable therapeutic strategy to increase the cytotoxicity of docetaxel for the treatment of advanced cSCC.