Illuminating biological pathways for drug targeting in head and neck squamous cell carcinoma
Autoři:
Gabrielle Choonoo aff001; Aurora S. Blucher aff001; Samuel Higgins aff002; Mitzi Boardman aff002; Sophia Jeng aff001; Christina Zheng aff001; James Jacobs aff001; Ashley Anderson aff006; Steven Chamberlin aff002; Nathaniel Evans aff002; Myles Vigoda aff003; Benjamin Cordier aff002; Jeffrey W. Tyner aff001; Molly Kulesz-Martin aff003; Shannon K. McWeeney aff001; Ted Laderas aff001
Působiště autorů:
Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, United States of America
aff001; Division of Bioinformatics and Computational Biology, Department of Medical Informatics & Clinical Epidemiology, Oregon Health & Science University, Portland, Oregon, United States of America
aff002; Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, Oregon, United States of America
aff003; Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, Oregon, United States of America
aff004; Pediatric Hematology and Oncology, OHSU Doernbecher Children’s Hospital, Portland, Oregon, United States of America
aff005; Department of Dermatology, Oregon Health & Science University, Portland, Oregon, United States of America
aff006; Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, Oregon, United States of America
aff007
Vyšlo v časopise:
PLoS ONE 14(10)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0223639
Souhrn
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.
Klíčová slova:
Cancer treatment – Drug discovery – Drug research and development – Head and neck squamous cell carcinoma – Human papillomavirus – Mutation – Radiation therapy – Somatic mutation
Zdroje
1. Union for International Cancer Control. Locally Advanced Squamous cell carcinoma of the head and neck [Internet]. World Health Organization; 2014. Available: https://www.who.int/selection_medicines/committees/expert/20/applications/HeadNeck.pdf
2. Cancer Facts & Figures 2018 [Internet]. American Cancer Society; 2018. Available: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2018/cancer-facts-and-figures-2018.pdf
3. Gillison ML. Evidence for a Causal Association Between Human Papillomavirus and a Subset of Head and Neck Cancers. Journal of the National Cancer Institute. 2000;92: 709–720. doi: 10.1093/jnci/92.9.709 10793107
4. Worsham MJ. Identifying the risk factors for late-stage head and neck cancer. Expert Rev Anticancer Ther. 2011;11: 1321–1325. doi: 10.1586/era.11.135 21929305
5. Gillison ML, D’Souza G, Westra W, Sugar E, Xiao W, Begum S, et al. Distinct Risk Factor Profiles for Human Papillomavirus Type 16–Positive and Human Papillomavirus Type 16–Negative Head and Neck Cancers. JNCI: Journal of the National Cancer Institute. 2008;100: 407–420. doi: 10.1093/jnci/djn025 18334711
6. Jung AC, Job S, Ledrappier S, Macabre C, Abecassis J, de Reynies A, et al. A Poor Prognosis Subtype of HNSCC Is Consistently Observed across Methylome, Transcriptome, and miRNome Analysis. Clinical Cancer Research. 2013;19: 4174–4184. doi: 10.1158/1078-0432.CCR-12-3690 23757353
7. Murphy BA, Ridner S, Wells N, Dietrich M. Quality of life research in head and neck cancer: a review of the current state of the science. Crit Rev Oncol Hematol. 2007;62: 251–267. doi: 10.1016/j.critrevonc.2006.07.005 17408963
8. Chin D, Boyle GM, Theile DR, Parsons PG, Coman WB. Molecular introduction to head and neck cancer (HNSCC) carcinogenesis. British Journal of Plastic Surgery. 2004;57: 595–602. doi: 10.1016/j.bjps.2004.06.010 15380692
9. Taberna M, Oliva M, Mesía R. Cetuximab-Containing Combinations in Locally Advanced and Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Front Oncol. 2019;9: 383. doi: 10.3389/fonc.2019.00383 31165040
10. Moskovitz J, Moy J, Ferris RL. Immunotherapy for Head and Neck Squamous Cell Carcinoma. Curr Oncol Rep. 2018;20: 22. doi: 10.1007/s11912-018-0654-5 29502288
11. National Cancer Institute. Targeted Cancer Therapies [Internet]. NIH; 2019. Available: https://www.cancer.gov/about-cancer/treatment/types/targeted-therapies/targeted-therapies-fact-sheet
12. Siu LL, Even C, Mesía R, Remenar E, Daste A, Delord J-P, et al. Safety and Efficacy of Durvalumab With or Without Tremelimumab in Patients With PD-L1–Low/Negative Recurrent or Metastatic HNSCC: The Phase 2 CONDOR Randomized Clinical Trial. JAMA Oncol. 2019;5: 195. doi: 10.1001/jamaoncol.2018.4628 30383184
13. Khatri P, Sirota M, Butte AJ. Ten Years of Pathway Analysis: Current Approaches and Outstanding Challenges. Ouzounis CA, editor. PLoS Computational Biology. 2012;8: e1002375. doi: 10.1371/journal.pcbi.1002375 22383865
14. Blucher AS, McWeeney SK, Stein L, Wu G. Visualization of drug target interactions in the contexts of pathways and networks with ReactomeFIViz. F1000Research. 2019;8: 908. doi: 10.12688/f1000research.19592.1 31372215
15. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proceedings of the National Academy of Sciences of the United States of America. 2005;102: 15545–15550. doi: 10.1073/pnas.0506580102 16199517
16. Grossman RL, Heath AP, Ferretti V, Varmus HE, Lowy DR, Kibbe WA, et al. Toward a Shared Vision for Cancer Genomic Data. N Engl J Med. 2016;375: 1109–1112. doi: 10.1056/NEJMp1607591 27653561
17. Ciriello G, Miller ML, Aksoy BA, Senbabaoglu Y, Schultz N, Sander C. Emerging landscape of oncogenic signatures across human cancers. Nat Genet. 2013;45: 1127–1133. doi: 10.1038/ng.2762 24071851
18. Perdomo S, Anantharaman D, Foll M, Abedi-Ardekani B, Durand G, Reis Rosa LA, et al. Genomic analysis of head and neck cancer cases from two high incidence regions. Langevin SM, editor. PLoS ONE. 2018;13: e0191701. doi: 10.1371/journal.pone.0191701 29377909
19. Gross AM, Orosco RK, Shen JP, Egloff AM, Carter H, Hofree M, et al. Multi-tiered genomic analysis of head and neck cancer ties TP53 mutation to 3p loss. Nat Genet. 2014;46: 939–943. doi: 10.1038/ng.3051 25086664
20. McLaren W, Gil L, Hunt SE, Riat HS, Ritchie GRS, Thormann A, et al. The Ensembl Variant Effect Predictor. Genome Biol. 2016;17: 122. doi: 10.1186/s13059-016-0974-4 27268795
21. Blucher AS, Choonoo G, Kulesz-Martin M, Wu G, McWeeney SK. Evidence-Based Precision Oncology with the Cancer Targetome. Trends in Pharmacological Sciences. 2017;38: 1085–1099. doi: 10.1016/j.tips.2017.08.006 28964549
22. Lehtonen S, Lehtonen E, Kudlicka K, Holthöfer H, Farquhar MG. Nephrin Forms a Complex with Adherens Junction Proteins and CASK in Podocytes and in Madin-Darby Canine Kidney Cells Expressing Nephrin. The American Journal of Pathology. 2004 Sep;165(3):923–36. doi: 10.1016/S0002-9440(10)63354-8 15331416
23. Lui VWY, Hedberg ML, Li H, Vangara BS, Pendleton K, Zeng Y, et al. Frequent mutation of the PI3K pathway in head and neck cancer defines predictive biomarkers. Cancer Discov. 2013;3: 761–769. doi: 10.1158/2159-8290.CD-13-0103 23619167
24. Fukusumi T, Califano JA. The NOTCH Pathway in Head and Neck Squamous Cell Carcinoma. J Dent Res. 2018;97: 645–653. doi: 10.1177/0022034518760297 29489439
25. Nyman PE, Buehler D, Lambert PF. Loss of Function of Canonical Notch Signaling Drives Head and Neck Carcinogenesis. Clin Cancer Res. 2018;24: 6308–6318. doi: 10.1158/1078-0432.CCR-17-3535 30087145
26. Lawrence MS, Sougnez C, Lichtenstein L, Cibulskis K, Lander E, Gabriel SB, et al. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015;517: 576–582. doi: 10.1038/nature14129 25631445
27. Zhou L, Zhao B, Zhang L, Wang S, Dong D, Lv H, et al. Alterations in Cellular Iron Metabolism Provide More Therapeutic Opportunities for Cancer. IJMS. 2018;19: 1545. doi: 10.3390/ijms19051545 29789480
28. Jung M, Mertens C, Tomat E, Brüne B. Iron as a Central Player and Promising Target in Cancer Progression. IJMS. 2019;20: 273. doi: 10.3390/ijms20020273 30641920
29. Teng MS, Brandwein-Gensler MS, Teixeira MS, Martignetti JA, Duffey DC. A study of TRAIL receptors in squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg. 2005;131: 407–412. doi: 10.1001/archotol.131.5.407 15897419
30. Chen J-J, Mikelis CM, Zhang Y, Gutkind JS, Zhang B. TRAIL induces apoptosis in oral squamous carcinoma cells—a crosstalk with oncogenic Ras regulated cell surface expression of death receptor 5. Oncotarget. 2013;4: 206–217. doi: 10.18632/oncotarget.813 23470485
31. Economopoulou P, Kotsantis I, Psyrri A. The promise of immunotherapy in head and neck squamous cell carcinoma: combinatorial immunotherapy approaches. ESMO Open. 2017;1: e000122. doi: 10.1136/esmoopen-2016-000122 28848660
32. Parfenov M, Pedamallu CS, Gehlenborg N, Freeman SS, Danilova L, Bristow CA, et al. Characterization of HPV and host genome interactions in primary head and neck cancers. Proceedings of the National Academy of Sciences. 2014;111: 15544–15549. doi: 10.1073/pnas.1416074111 25313082
33. Iorio F, Knijnenburg TA, Vis DJ, Bignell GR, Menden MP, Schubert M, et al. A Landscape of Pharmacogenomic Interactions in Cancer. Cell. 2016;166: 740–754. doi: 10.1016/j.cell.2016.06.017 27397505
34. Scheckenbach K, Wagenmann M, Freund M, Schipper J, Hanenberg H. Squamous cell carcinomas of the head and neck in Fanconi anemia: risk, prevention, therapy, and the need for guidelines. Klin Padiatr. 2012;224: 132–138. doi: 10.1055/s-0032-1308989 22504776
35. Velleuer E, Dietrich R. Fanconi anemia: young patients at high risk for squamous cell carcinoma. Mol Cell Pediatr. 2014;1: 9. doi: 10.1186/s40348-014-0009-8 26567103
36. Furquim CP, Pivovar A, Amenábar JM, Bonfim C, Torres-Pereira CC. Oral cancer in Fanconi anemia: Review of 121 cases. Critical Reviews in Oncology/Hematology. 2018;125: 35–40. doi: 10.1016/j.critrevonc.2018.02.013 29650274
37. Gillison ML, Akagi K, Xiao W, Jiang B, Pickard RKL, Li J, et al. Human papillomavirus and the landscape of secondary genetic alterations in oral cancers. Genome Res. 2019;29: 1–17. doi: 10.1101/gr.241141.118 30563911
38. Brand TM, Hartmann S, Bhola NE, Li H, Zeng Y, O’Keefe RA, et al. Cross-talk Signaling between HER3 and HPV16 E6 and E7 Mediates Resistance to PI3K Inhibitors in Head and Neck Cancer. Cancer Res. 2018;78: 2383–2395. doi: 10.1158/0008-5472.CAN-17-1672 29440171
39. Eckhardt M, Zhang W, Gross AM, Von Dollen J, Johnson JR, Franks-Skiba KE, et al. Multiple Routes to Oncogenesis Are Promoted by the Human Papillomavirus–Host Protein Network. Cancer Discov. 2018;8: 1474–1489. doi: 10.1158/2159-8290.CD-17-1018 30209081
40. Palmer AC, Sorger PK. Combination Cancer Therapy Can Confer Benefit via Patient-to-Patient Variability without Drug Additivity or Synergy. Cell. 2017;171: 1678–1691.e13. doi: 10.1016/j.cell.2017.11.009 29245013
41. McLornan DP, List A, Mufti GJ. Applying synthetic lethality for the selective targeting of cancer. N Engl J Med. 2014;371: 1725–1735. doi: 10.1056/NEJMra1407390 25354106
42. Ferrari E, Lucca C, Foiani M. A lethal combination for cancer cells: synthetic lethality screenings for drug discovery. Eur J Cancer. 2010;46: 2889–2895. doi: 10.1016/j.ejca.2010.07.031 20724143
43. Kurtz SE, Eide CA, Kaempf A, Khanna V, Savage SL, Rofelty A, et al. Molecularly targeted drug combinations demonstrate selective effectiveness for myeloid- and lymphoid-derived hematologic malignancies. PNAS. 2017;114: E7554–E7563. doi: 10.1073/pnas.1703094114 28784769
44. Hedberg ML, Peyser ND, Bauman JE, Gooding WE, Li H, Bhola NE, et al. Use of nonsteroidal anti-inflammatory drugs predicts improved patient survival for PIK3CA -altered head and neck cancer. J Exp Med. 2019; jem.20181936. doi: 10.1084/jem.20181936 30683736
45. Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, et al. Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal. Science Signaling. 2013;6: pl1–pl1. doi: 10.1126/scisignal.2004088 23550210
46. Nulton TJ, Olex AL, Dozmorov M, Morgan IM, Windle B. Analysis of The Cancer Genome Atlas sequencing data reveals novel properties of the human papillomavirus 16 genome in head and neck squamous cell carcinoma. Oncotarget. 2017;8: 17684–17699. doi: 10.18632/oncotarget.15179 28187443
47. Higgins S. Drug sensitivities in the context of genomic aberrations: applications to cancer. Oregon Health & Science University. 2016; doi: 10.6083/m48k7732
48. Benjamini Y, Yekutieli D. The control of the false discovery rate in multiple testing under dependency. Annals of Stat. 2001;29: 1165–1188.
49. Wu G, Dawson E, Duong A, Haw R, Stein L. ReactomeFIViz: a Cytoscape app for pathway and network-based data analysis. F1000Res. 2014;3: 146. doi: 10.12688/f1000research.4431.2 25309732
50. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13: 2498–2504. doi: 10.1101/gr.1239303 14597658
Článek vyšel v časopise
PLOS One
2019 Číslo 10
- S diagnostikou Parkinsonovy nemoci může nově pomoci AI nástroj pro hodnocení mrkacího reflexu
- Je libo čepici místo mozkového implantátu?
- Pomůže v budoucnu s triáží na pohotovostech umělá inteligence?
- AI může chirurgům poskytnout cenná data i zpětnou vazbu v reálném čase
- Nová metoda odlišení nádorové tkáně může zpřesnit resekci glioblastomů
Nejčtenější v tomto čísle
- Correction: Low dose naltrexone: Effects on medication in rheumatoid and seropositive arthritis. A nationwide register-based controlled quasi-experimental before-after study
- Combining CDK4/6 inhibitors ribociclib and palbociclib with cytotoxic agents does not enhance cytotoxicity
- Experimentally validated simulation of coronary stents considering different dogboning ratios and asymmetric stent positioning
- Risk factors associated with IgA vasculitis with nephritis (Henoch–Schönlein purpura nephritis) progressing to unfavorable outcomes: A meta-analysis
Zvyšte si kvalifikaci online z pohodlí domova
Všechny kurzy