Journal article

Stage-dependent therapeutic efficacy in PI3K/mTOR-driven squamous cell carcinoma of the skin

Charbel Darido, Smitha R Georgy, Carleen Cullinane, Darren D Partridge, Rachael Walker, Seema Srivastava, Suraya Roslan, Marina R Carpinelli, Sebastian Dworkin, Richard B Pearson, Stephen M Jane

CELL DEATH AND DIFFERENTIATION | NATURE PUBLISHING GROUP | Published : 2018

Abstract

Cutaneous squamous cell carcinoma (SCC) is a recurrent cancer that is prevalent in predisposed subjects such as immunosuppressed patients and patients being treated for other malignancies. Model systems to trial therapies at different stages of SCC development are lacking, therefore precluding efficient therapeutic interventions. Here, we have disrupted the expression of the tumor suppressor GRHL3 to induce loss of PTEN and activation of the PI3K/mTOR signaling pathway in mice and human skin, promoting aggressive SCC development. We then examined the potential for targeting PI3K/mTOR and an oncogenic driver miR-21, alone and in combination, for the prevention and treatment of SCC during the ..

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Grants

Awarded by Australian National Health and Medical Research (NHMRC)


Awarded by Victorian Cancer Agency


Awarded by The Association for International Cancer Research (AICR)


Awarded by Victorian Cancer Agency Mid-Career Fellowship


Awarded by Novartis (Basel, Switzerland)


Funding Acknowledgements

This study was supported by the Australian National Health and Medical Research (NHMRC, APP1049870, APP1106697). CD was supported by a fellowship from the Victorian Cancer Agency (Clare Oliver Memorial, COF11_04) and by a grant (11-0060) from The Association for International Cancer Research (AICR). RBP is supported by an NHMRC Research fellowship and CD is currently holding a Victorian Cancer Agency Mid-Career Fellowship (CR_16/5985). NVP-BEZ235 and NVP-BKM120 were obtained from Novartis (Basel, Switzerland). We thank Susan Jackson and Kerry Ardley for animal technical support and Dr Andrew Cuddihy for his critical reading and correction of the manuscript.