The repurposed drug IHN109 identified in the AcceleraTED platform is a promising candidate for treatment of Head and Neck cancer

A. Franke^1,2, J. L. Bryant³, G. B. Ryan³, M. Hartley³, R. J. Spruce³, H. Mehanna³, N. Batis³. ¹Universitaet zu Luebeck, Luebeck, Germany, ²InHANSE, Institute of Cancer and Genetic Sciences, University of Birmingham, Birmingham, United Kingdom, ³InHANSE, Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom.

Introduction: Worldwide, more than 300 000 people die from head and neck cancer (HNC) each year making it the 6^th most common type of cancer (1). The considerable side effects of current treatment and poor prognosis highlight the urgent need for novel treatments. The AcceleraTED platform has proven to be a useful tool for identifying repurposed and new drugs in treating HNC. It consists of several stages; Stage 1: high throughput screening assays on a representative HNC cell line panel; Stage 2: validation by additional in vitro assays on both cell lines and primary cultures; Stage 3: validation of in vitro findings using xenograft animal models; Stage 4: initiating and running early to late phase clinical trials. The antimalarial drug IHN109 has been identified as a positive hit in stage 1 and was further proceeded through the platform. The overall aims of this study were to identify a lead drug in the AcceleraTED platform and to show its in vitro and in vivo anti-cancer activity.

Methods: Quantitative measurements of cell proliferation were performed using the AlamarBlue cell viability assay. Cells were seeded at appropriate optimised cell densities in 96 well-plates 24hrs prior to drug treatment. Appropriate drug treatments were added to triplicate wells and incubated for 68hrs at 37^oC. 4hrs prior to measurement, 20μl AlamarBlue reagent was added per well and cells were further incubated at 37^oC. Measurements were performed using 550/590nm fluorescence counter. All RFU values were normalised by subtracting values from paired media-only plates. The concentrations used for IHN109 range from 1.3x10^-7M-8x10^-6M.

Results: We demonstrate that IHN109 is able to reduce cell viability in 3 different cell lines (HPV-negative CAL27, SCC040; HPV-positive SCC047) in a concentration dependent manner alone and in combination with cisplatin (Fig.1; n=3). IHN109 enhances cisplatin’s inhibitory effect on cell viability in established cell lines and patient derived primary cells (Fig.2; n=3-4) in a concentration dependent manner; whilst maintaining cisplatin’s concentration dependent effect. Moreover, IHN109 exhibits anti-colony forming potential comparable to standard of care treatment cisplatin and irradiation (data not shown).

Summary: IHN109 is a promising drug for the treatment of HNC. We established its anti-viability potential in both HNC cell lines and primary cells, as well as its anti-colony forming activity in a concentration dependent manner. The potential mode of action and in vivo tolerability are currently being investigated.

References:

(1) Fung C and Grandis JR (2010). Expert Opin Emerg Drugs 15(3): 355-373.