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: 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

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

Léčba bolesti v ordinaci praktického lékaře
nový kurz
Autoři: MUDr. PhDr. Zdeňka Nováková, Ph.D.

Revmatoidní artritida: včas a k cíli
Autoři: MUDr. Heřman Mann

Jistoty a nástrahy antikoagulační léčby aneb kardiolog - neurolog - farmakolog - nefrolog - právník diskutují
Autoři: doc. MUDr. Štěpán Havránek, Ph.D., prof. MUDr. Roman Herzig, Ph.D., doc. MUDr. Karel Urbánek, Ph.D., prim. MUDr. Jan Vachek, MUDr. et Mgr. Jolana Těšínová, Ph.D.

Léčba akutní pooperační bolesti
Autoři: doc. MUDr. Jiří Málek, CSc.

Nové antipsychotikum kariprazin v léčbě schizofrenie
Autoři: prof. MUDr. Cyril Höschl, DrSc., FRCPsych.

Všechny kurzy
Kurzy Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se