Illuminating biological pathways for drug targeting in head and neck squamous cell carcinoma

Gabrielle Choonoo, Aurora S. Blucher, Samuel Higgins, Mitzi Boardman, Sophia Jeng, Christina Zheng, James Jacobs, Ashley Anderson, Steven Chamberlin, Nathaniel Evans, Myles Vigoda, Benjamin Cordier, Jeffrey W. Tyner, Molly Kulesz-Martin, Shannon K. McWeeney, Ted Laderas

Research output: Contribution to journalArticle

Abstract

Head and neck squamous cell carcinoma (HNSCC) remains a morbid disease with poor prognosis and treatment that typically leaves patients with permanent damage to critical functions such as eating and talking. Currently only three targeted therapies are FDA approved for use in HNSCC, two of which are recently approved immunotherapies. In this work, we identify biological pathways involved with this disease that could potentially be targeted by current FDA approved cancer drugs and thereby expand the pool of potential therapies for use in HNSCC treatment. We analyzed 508 HNSCC patients with sequencing information from the Genomic Data Commons (GDC) database and assessed which biological pathways were significantly enriched for somatic mutations or copy number alterations. We then further classified pathways as either “light” or “dark” to the current reach of FDA-approved cancer drugs using the Cancer Targetome, a compendium of drug-target information. Light pathways are statistically enriched with somatic mutations (or copy number alterations) and contain one or more targets of current FDA-approved cancer drugs, while dark pathways are enriched with somatic mutations (or copy number alterations) but not currently targeted by FDA-approved cancer drugs. Our analyses indicated that approximately 35–38% of disease-specific pathways are in scope for repurposing of current cancer drugs. We further assess light and dark pathways for subgroups of patient tumor samples according to HPV status. The framework of light and dark pathways for HNSCC-enriched biological pathways allows us to better prioritize targeted therapies for further research in HNSCC based on the HNSCC genetic landscape and FDA-approved cancer drug information. We also highlight the importance in the identification of sub-pathways where targeting and cross targeting of other pathways may be most beneficial to predict positive or negative synergy with potential clinical significance. This framework is ideal for precision drug panel development, as well as identification of highly aberrant, untargeted candidates for future drug development.

Original languageEnglish (US)
Article numbere0223639
JournalPloS one
Volume14
Issue number10
DOIs
StatePublished - Jan 1 2019

Fingerprint

squamous cell carcinoma
Drug Delivery Systems
neck
drugs
neoplasms
Pharmaceutical Preparations
somatic mutation
Neoplasms
Light
therapeutics
Mutation
Therapeutics
Carcinoma, squamous cell of head and neck
Epithelial Cells
immunotherapy
Immunotherapy
prognosis
Tumors
Eating
ingestion

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Choonoo, G., Blucher, A. S., Higgins, S., Boardman, M., Jeng, S., Zheng, C., ... Laderas, T. (2019). Illuminating biological pathways for drug targeting in head and neck squamous cell carcinoma. PloS one, 14(10), [e0223639]. https://doi.org/10.1371/journal.pone.0223639

Illuminating biological pathways for drug targeting in head and neck squamous cell carcinoma. / Choonoo, Gabrielle; Blucher, Aurora S.; Higgins, Samuel; Boardman, Mitzi; Jeng, Sophia; Zheng, Christina; Jacobs, James; Anderson, Ashley; Chamberlin, Steven; Evans, Nathaniel; Vigoda, Myles; Cordier, Benjamin; Tyner, Jeffrey W.; Kulesz-Martin, Molly; McWeeney, Shannon K.; Laderas, Ted.

In: PloS one, Vol. 14, No. 10, e0223639, 01.01.2019.

Research output: Contribution to journalArticle

Choonoo, G, Blucher, AS, Higgins, S, Boardman, M, Jeng, S, Zheng, C, Jacobs, J, Anderson, A, Chamberlin, S, Evans, N, Vigoda, M, Cordier, B, Tyner, JW, Kulesz-Martin, M, McWeeney, SK & Laderas, T 2019, 'Illuminating biological pathways for drug targeting in head and neck squamous cell carcinoma', PloS one, vol. 14, no. 10, e0223639. https://doi.org/10.1371/journal.pone.0223639
Choonoo, Gabrielle ; Blucher, Aurora S. ; Higgins, Samuel ; Boardman, Mitzi ; Jeng, Sophia ; Zheng, Christina ; Jacobs, James ; Anderson, Ashley ; Chamberlin, Steven ; Evans, Nathaniel ; Vigoda, Myles ; Cordier, Benjamin ; Tyner, Jeffrey W. ; Kulesz-Martin, Molly ; McWeeney, Shannon K. ; Laderas, Ted. / Illuminating biological pathways for drug targeting in head and neck squamous cell carcinoma. In: PloS one. 2019 ; Vol. 14, No. 10.
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