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. 2018 May 25;9(40):26064-26071.
doi: 10.18632/oncotarget.25436.

High-throughput testing in head and neck squamous cell carcinoma identifies agents with preferential activity in human papillomavirus-positive or negative cell lines

Farhad Ghasemi #  1 , Morgan Black #  1   2 , Ren X Sun  3   4 , Frederick Vizeacoumar  5 , Nicole Pinto  1   2 , Kara M Ruicci  1   2 , John Yoo  1   2 , Kevin Fung  1   2 , Danielle MacNeil  1   2 , David A Palma  2 , Eric Winquist  2 , Joe S Mymryk  1   2   6 , Laurie A Ailles  7 , Alessandro Datti  8   9 , John W Barrett #  1   2 , Paul C Boutros #  3   4   7 , Anthony C Nichols #  1   2
Affiliations

High-throughput testing in head and neck squamous cell carcinoma identifies agents with preferential activity in human papillomavirus-positive or negative cell lines

Farhad Ghasemi et al. Oncotarget. .

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a common cancer diagnosis worldwide. Despite advances in treatment, HNSCC has very poor survival outcomes, emphasizing an ongoing need for development of improved therapeutic options. The distinct tumor characteristics of human papillomavirus (HPV)-positive vs. HPV-negative disease necessitate development of treatment strategies tailored to tumor HPV-status. High-throughput robotic screening of 1,433 biologically and pharmacologically relevant compounds at a single dose (4 μM) was carried out against 6 HPV-positive and 20 HPV-negative HNSCC cell lines for preliminary identification of therapeutically relevant compounds. Statistical analysis was further carried out to differentiate compounds with preferential activity against cell lines stratified by the HPV-status. These analyses yielded 57 compounds with higher activity in HPV-negative cell lines, and 34 with higher-activity in HPV-positive ones. Multi-point dose-response curves were generated for six of these compounds (Ryuvidine, MK-1775, SNS-032, Flavopiridol, AZD-7762 and ARP-101), confirming Ryuvidine to have preferential potency against HPV-negative cell lines, and MK-1775 to have preferential potency against HPV-positive cell lines. These data comprise a valuable resource for further investigation of compounds with therapeutic potential in the HNSCC.

Keywords: cell lines; chemotherapy; head and neck cancer; high throughput drug testing; human papillomavirus.

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Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no potential conflicts of interest.

Figures

Figure 1
Figure 1. The top 20 most potent drugs and determined by the B-score in HNSCC cell lines
from the Kinase inhibitor (A) and Tocris (B) panels in the high-throughput drug screen.
Figure 2
Figure 2. Top 10 drugs
with (A) HPV-positive and (B) HPV-negative selective potency from Kinase inhibitor and Tocris compound panels.
Figure 3
Figure 3. Drug potency validation studies revealed
(A) Ryuvidine to be selective against HPV-negative cell lines (** p=0.003) and (B) MK-1775 to be selective against HPV-positive cell lines (* p=0.03).
See this image and copyright information in PMC

References

    1. Nichols AC, Palma DA, Dhaliwal SS, Tan S, Theuer J, Chow W, Rajakumar C, Um S, Mundi N, Berk S, Zhou R, Basmaji J, Rizzo G, et al. The epidemic of human papillomavirus and oropharyngeal cancer in a Canadian population. Curr Oncol. 2013;20:212–9. https://doi.org/10.3747/co.20.1375 - DOI - PMC - PubMed
    1. Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, Jiang B, Goodman MT, Sibug-Saber M, Cozen W, Liu L, Lynch CF, Wentzensen N, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011;29:4294–301. https://doi.org/10.1200/JCO.2011.36.4596 - DOI - PMC - PubMed
    1. Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363:24–35. https://doi.org/10.1056/NEJMoa0912217 - DOI - PMC - PubMed
    1. Cancer Genome Atlas Network Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015;517:576–82. https://doi.org/10.1038/nature14129 - DOI - PMC - PubMed
    1. Gazdar AF, Girard L, Lockwood WW, Lam WL, Minna JD. Lung cancer cell lines as tools for biomedical discovery and research. J Natl Cancer Inst. 2010;102:1310–21. https://doi.org/10.1093/jnci/djq279 - DOI - PMC - PubMed