High Throughput Drug Testing Identifies Agents with Selective Activity in HPV-Positive and HPV-Negative Cell Lines

Presentation: C004
Topic: Immunotherapy and Other Adjuvant Treatments
Type: Poster
Date: Thursday, April 19, 2018
Session: 9:00 AM - 7:00 PM
Authors: Farhad Ghasemi, BSc1, Morgan D Black, BSc, MSc1, Alessandro Datti, PhD2, John W Barrett, PhD1, John Yoo, MD1, Kevin Fung, MD1, S D MacNeil, MD, MSc1, Anthony C Nichols, MD1
Institution(s): 1Western University, 2Lunenfeld Tanenbaum Research Institute

Background: Head and neck squamous cell carcinoma (HNSCC) is the 5th most common cancer worldwide.  Human papillomavirus (HPV)-positive and HPV-negative HNSCC have distinct molecular and clinical features suggesting the need to develop therapeutics tailored to each cancer type.  

Methods: High throughput robotic testing of 1400 compounds at a single dose of 4uM was carried out against 6 HPV-positive and 20 HPV-negative HNSCC cell lines. Statistical analysis identified compounds with preferential activity against cell lines stratified by the HPV-status after accounting for the false discovery rate.  Drug potency validation studies were then carried out with a subset of the identified compounds at a concentration range of 10 nM to 100 µM against 8 HPV-positive and 11 HPV-negative cell lines.

Results Twenty drugs were identified with preferential activity in either HPV-positive or HPV-negative cell lines based on the single dose experiments.  Dose response curves were generated for six of these drugs confirming preferential activity of one drug in HPV-positive lines and two drugs in HPV-negative lines.  

Conclusion: High throughput drug testing successfully identified therapeutic agents with selective activity for both HPV-positive and HPV-negative cells lines.  These findings require in vivo confirmation prior to proceeding to clinical trials, however they have the potential to facilitate targeted treatment of these distinct cancer types.