Investigational multitargeted kinase inhibitors in development for head and neck neoplasms

References

• Vigneswaran N, Williams MD. Epidemiological trends in head and neck cancer and aids in diagnosis. Oral Maxillofac Surg Clin North Am. 2014;26(2):123–141.
   PubMed Web of Science ®Google Scholar
• Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7–30.
   PubMed Web of Science ®Google Scholar
• Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363:24–35.
   PubMed Web of Science ®Google Scholar
• Denaro N, Russi EG, Adamo V, Merlano MC. State-of-the-art and emerging treatment options in the management of head and neck cancer: news from 2013. Oncology. 2014;86:212–229.
   PubMed Web of Science ®Google Scholar
• Marur S, Forastiere AA. Head and neck squamous cell carcinoma: update on epidemiology, diagnosis, and treatment. Mayo Clin Proc. 2016;91(3):386–396.
   PubMed Web of Science ®Google Scholar
• Kozakiewicz P, Grzybowska-Szatkowska L. Application of molecular targeted therapies in the treatment of head and neck squamous cell carcinoma. Oncol Lett. 2018;15(5):7497–7505.
   PubMed Web of Science ®Google Scholar
• Blume-Jensen P, Hunter T. Oncogenic kinase signaling. Nature. 2001;411:355–365.
   PubMed Web of Science ®Google Scholar
• Cohen EE, Lingen MW, Vokes EE. The expanding role of systemic therapy in head and neck cancer. J Clin Oncol. 2004;22(9):1743–1752.
   PubMed Web of Science ®Google Scholar
• Price KA, Cohen EE. Current treatment options for metastatic head and neck cancer. Curr Treat Options Oncol. 2012;13:35–46.
   PubMed Web of Science ®Google Scholar
• Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006;354:567–578.
   PubMed Web of Science ®Google Scholar
• Ferris RL, Blumenschein G, Fayette J, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375(19):1856–1867.
   PubMed Web of Science ®Google Scholar
• Sheth S, Weiss J. Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. Future Oncol. 2018;14(16):1547–1558.
   PubMed Web of Science ®Google Scholar
• Vermorken JB, Trigo J, Hitt R, et al. Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. J Clin Oncol. 2007;25(16):2171–2177.
   PubMed Web of Science ®Google Scholar
• Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008;359(11):1116–1127.
   PubMed Web of Science ®Google Scholar
• Seiwert TY, Burtness B, Mehra R, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Lancet Oncol. 2016;17(7):956–965.
   PubMed Web of Science ®Google Scholar
• Lemmon MA, Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell. 2010;141(7):1117–1134.
   PubMed Web of Science ®Google Scholar
• Arora A, Scholar EM. Role of tyrosine kinase inhibitors in cancer therapy. J Pharmacol Exp Ther. 2005;315(3):971–979.
   PubMed Web of Science ®Google Scholar
• Anastassiadis T, Deacon SW, Devarajan K. Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol. 2011;29(11):1039–1045.
   PubMed Web of Science ®Google Scholar
• Davis MI, Hunt JP, Herrgard S. Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol. 2011;29(11):1046–1051.
   PubMed Web of Science ®Google Scholar
• Klaeger S, Heinzlmeir S, Wilhelm M, et al. The target landscape of clinical kinase drugs. Science. 2017;358(6367):eaan4368.
   PubMed Web of Science ®Google Scholar
• U.S. Food & Drug Administration. New drugs at FDA: CDER’s new molecular entities and new therapeutic biological products.FDA; 2018. Available from: https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/ucm592464.htm.
   Google Scholar
• Ferguson FM, Gray NS. Kinase inhibitors: the road ahead. Nat Rev Drug Discov. 2018;17(5):353–377.
   PubMed Web of Science ®Google Scholar
• Steeghs N, Nortier JW, Gefllderblom H. Small molecule tyrosine kinase inhibitors in the treatment of solid tumors: an update of recent developments. Ann Surg Oncol. 2007;14(2):942–953.
   PubMed Web of Science ®Google Scholar
• Chun PY, Feng FY, Scheurer AM, et al. Synergistic effects of gemcitabine and gefitinib in the treatment of head and neck carcinoma. Cancer Res. 2006;66(2):981–988.
   PubMed Web of Science ®Google Scholar
• Wheeler DL, Dunn EF, Harari PM. Understanding resistance to EGFR inhibitors—impact on future treatment strategies. Nat Rev Clin Oncol. 2010;7(9):493–507.
   PubMed Web of Science ®Google Scholar
• Taneja C, Allen H, Koness RJ, et al. Changing patterns of failure of head and neck cancer. Arch Otolaryngol Head Neck Surg. 2002;128(3):324–327.
   PubMedGoogle Scholar
• Grandis JR, Tweardy DJ. Elevated levels of transforming growth factor α and epidermal growth factor receptor messenger RNA are early markers of carcinogenesis in head and neck cancer. Cancer Res. 1993;53(15):3579–3584.
   PubMed Web of Science ®Google Scholar
• Molinolo AA, Amornphimoltham P, Squarize CH, et al. Dysregulated molecular networks in head and neck carcinogenesis. Oral Oncol. 2009;45(4–5):324–334.
   PubMed Web of Science ®Google Scholar
• Onita B, Lester DRT, Iman AA, et al. Comparison of high-dose cisplatin-based chemoradiotherapy and cetuximab-based bioradiotherapy for p16-positive oropharyngeal squamous cell carcinoma in the context of revised HPV-based staging. Rep Pract Oncol Radiother. 2018;23(5):451–457.
   PubMedGoogle Scholar
• Brand TM, Iida M, Wheeler DL. Molecular mechanisms of resistance to the EGFR monoclonal antibody cetuximab. Cancer Biol Ther. 2011;11(9):777–792.
   PubMed Web of Science ®Google Scholar
• Madoz-Gúrpide J, Zazo S, Chamizo C, et al. Activation of MET pathway predicts poor outcome to cetuximab in patients with recurrent or metastatic head and neck cancer. J Transl Med. 2015;13(1):282.
   PubMedGoogle Scholar
• Jiang N, Wang D, Hu Z, et al. Combination of anti‐HER3 antibody MM‐121/SAR256212 and cetuximab inhibits tumor growth in preclinical models of head and neck squamous cell carcinoma. Mol Cancer Ther. 2014;13:1826‐1836.
   Web of Science ®Google Scholar
• Wheeler DL, Huang S, Kruser TJ, et al. Mechanisms of acquired resistance to cetuximab: role of HER (ErbB) family members. Oncogene. 2008;27(28):3944–3956.
   PubMed Web of Science ®Google Scholar
• Yen L, Benlimame N, Nie Z, et al. Differential regulation of tumor angiogenesis by distinct ErbB homo-and heterodimers. Mol Biol Cell. 2002;13(11):4029–4044.
   PubMed Web of Science ®Google Scholar
• Bertotti A, Migliardi G, Galimi F, et al. A molecularly annotated platform of patient-derived xenografts (‘xenopatients’) identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer. Cancer Discov. 2011;1(6):508–523.
   PubMed Web of Science ®Google Scholar
• Bardelli A, Corso S, Bertotti A, et al. Amplification of the MET receptor drives resistance to anti-EGFR therapies in colorectal cancer. Cancer Discov. 2013;3(6):658–673.
   PubMed Web of Science ®Google Scholar
• Hu S, Fu W, Xu W, et al. Four-in-one antibodies have superior cancer inhibitory activity against EGFR, HER2, HER3, and VEGF through disruption of HER/MET crosstalk. Cancer Res. 2015;75(1):159–170.
   PubMed Web of Science ®Google Scholar
• Hirsch FR, Sequist LV, Gore I, et al. Long‐term safety and survival with gefitinib in select patients with advanced non–small cell lung cancer: results from the US IRESSA clinical access program (ICAP). Cancer. 2018;124(11):2407–2414.
   PubMed Web of Science ®Google Scholar
• Stewart JS, Cohen EE, Licitra L, et al. Phase III study of gefitinib compared with intravenous methotrexate for recurrent squamous cell carcinoma of the head and neck. J Clin Oncol. 2009;27(11):1864–1871.
   PubMed Web of Science ®Google Scholar
• Dutton SJ, Ferry DR, Blazeby JM, et al. Gefitinib for oesophageal cancer progressing after chemotherapy (COG): A phase 3, multicentre, double-blind, placebo-controlled randomised trial. Lancet Oncol. 2014;15(8):894–904.
   PubMed Web of Science ®Google Scholar
• Martins RG, Parvathaneni U, Bauman JE, et al. Cisplatin and radiotherapy with or without erlotinib in locally advanced squamous cell carcinoma of the head and neck: A randomized phase II trial. J Clin Oncol. 2013;31(11):1415–1421.
   PubMed Web of Science ®Google Scholar
• Weiss JM, Bagley S, Hwang W, et al. Capecitabine and lapatinib for the first-line treatment of metastatic/recurrent head and neck squamous cell carcinoma. Cancer. 2016;122(15):2350–2355.
   PubMed Web of Science ®Google Scholar
• Harrington K, Temam S, Mehanna H, et al. Postoperative adjuvant lapatinib and concurrent chemoradiotherapy followed by maintenance lapatinib monotherapy in high-risk patients with resected squamous cell carcinoma of the head and neck: A phase III, randomized, double-blind, placebo-controlled study. J Clin Oncol. 2015;33(35):4202–4209.
   PubMed Web of Science ®Google Scholar
• Weiss JM, Grilley‐Olson JE, Deal AM, et al. Phase 2 trial of neoadjuvant chemotherapy and transoral endoscopic surgery with risk‐adapted adjuvant therapy for squamous cell carcinoma of the head and neck. Cancer. 2018;124(14):2986–2992.
   PubMed Web of Science ®Google Scholar
• Young NR, Soneru C, Liu J, et al. Afatinib efficacy against squamous cell carcinoma of the head and neck cell lines in vitro and in vivo. Target Oncol. 2015;10(4):501–508.
   PubMed Web of Science ®Google Scholar
• Machiels J, Bossi P, Menis J, et al. Activity and safety of afatinib in a window preoperative EORTC study in patients with squamous cell carcinoma of the head and neck (SCCHN). Ann Oncol. 2018;29(4):985–991.
   PubMed Web of Science ®Google Scholar
• Cohen EE, Licitra LF, Burtness B, et al. Biomarkers predict enhanced clinical outcomes with afatinib versus methotrexate in patients with second-line recurrent and/or metastatic head and neck cancer. Ann Oncol. 2017;28(10):2526–2532.
   PubMed Web of Science ®Google Scholar
• Specenier P, Vermorken J. Afatinib in squamous cell carcinoma of the head and neck. Expert Opin Pharmacother. 2016;17(9):1295–1301.
   PubMed Web of Science ®Google Scholar
• Wilhelm SM, Carter C, Tang L, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004;64(19):7099–7109.
   PubMed Web of Science ®Google Scholar
• Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378–390.
   PubMed Web of Science ®Google Scholar
• Laban S, Steinmeister L, Gleibner L, et al. Sorafenib sensitizes head and neck squamous cell carcinoma cells to ionizing radiation. Radiother Oncol. 2013;109(2):286–292.
   PubMed Web of Science ®Google Scholar
• Affolter A, Samosny G, Heimes A, et al. Multikinase inhibitors sorafenib and sunitinib as radiosensitizers in head and neck cancer cell lines. Head Neck. 2017;39(4):623–632.
   PubMed Web of Science ®Google Scholar
• Williamson SK, Moon J, Huang CH, et al. Phase II evaluation of sorafenib in advanced and metastatic squamous cell carcinoma of the head and neck: southwest Oncology Group Study S0420. J Clin Oncol. 2010;28(20):3330–3335.
   PubMed Web of Science ®Google Scholar
• Gilbert J, Schell MJ, Zhao X, et al. A randomized phase II efficacy and correlative studies of cetuximab with or without sorafenib in recurrent and/or metastatic head and neck squamous cell carcinoma. Oral Oncol. 2015;51(4):376–382.
   PubMed Web of Science ®Google Scholar
• Faivre S, Delbaldo C, Vera K, et al. Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J Clin Oncol. 2006;24(1):25–35.
   PubMed Web of Science ®Google Scholar
• Hillman GG, Singh-Gupta V, Al-Bashir AK, et al. Monitoring sunitinib-induced vascular effects to optimize radiotherapy combined with soy isoflavones in murine xenograft tumor. Transl Oncol. 2011;4(2):110–121.
   PubMed Web of Science ®Google Scholar
• Matsumoto S, Batra S, Saito K, et al. Anti-angiogenic agent sunitinib transiently increases tumor oxygenation and suppresses cycling hypoxia. Cancer Res. 2011;71(20):6350–6359.
   PubMed Web of Science ®Google Scholar
• Choong NW, Kozloff M, Taber D, et al. Phase II study of sunitinib malate in head and neck squamous cell carcinoma. Invest New Drugs. 2010;28(5):677–683.
   PubMed Web of Science ®Google Scholar
• Bozec A, Sudaka A, Toussan N, et al. Combination of sunitinib, cetuximab and irradiation in an orthotopic head and neck cancer model. Ann Oncol. 2009;20(10):1703–1707.
   PubMed Web of Science ®Google Scholar
• Sano D, Matsumoto F, Valdecanas D, et al. Vandetanib restores head and neck squamous cell carcinoma cells’ sensitivity to cisplatin and radiation in vivo and in vitro. Clin Cancer Res. 2011;17(7):1815–1827.
   PubMed Web of Science ®Google Scholar
• Gustafson DL, Frederick B, Merz AL, et al. Dose scheduling of the dual VEGFR and EGFR tyrosine kinase inhibitor vandetanib (ZD6474, Zactima®) in combination with radiotherapy in EGFR-positive and EGFR-null human head and neck tumor xenografts. Cancer Chemother Pharmacol. 2008;61(2):179–188.
   PubMed Web of Science ®Google Scholar
• Papadimitrakopoulou VA, Frank SJ, Cohen EW, et al. Phase I study of vandetanib with radiation therapy with or without cisplatin in locally advanced head and neck squamous cell carcinoma. Head Neck. 2016;38(3):439–447.
   PubMed Web of Science ®Google Scholar
• Limaye S, Riley S, Zhao S, et al. A randomized phase II study of docetaxel with or without vandetanib in recurrent or metastatic squamous cell carcinoma of head and neck (SCCHN). Oral Oncol. 2013;49(8):835–841.
   PubMed Web of Science ®Google Scholar
• Van Cruijsen H, Giaccone G, Hoekman K. Epidermal growth factor receptor and angiogenesis: opportunities for combined anticancer strategies. Int J Cancer. 2005;117(6):883–888.
   PubMed Web of Science ®Google Scholar
• Viloria-Petit A, Crombet T, Jothy S, et al. Acquired resistance to the antitumor effect of epidermal growth factor receptor-blocking antibodies in vivo: A role for altered tumor angiogenesis. Cancer Res. 2001;61(13):5090–5101.
   PubMed Web of Science ®Google Scholar
• Motz GT, Coukos G. The parallel lives of angiogenesis and immunosuppression: cancer and other tales. Nat Rev Immunol. 2011;11(10):702–711.
   PubMed Web of Science ®Google Scholar
• Schmittnaegel M, Rigamonti N, Kadioglu E, et al. Dual angiopoietin-2 and VEGFA inhibition elicits antitumor immunity that is enhanced by PD-1 checkpoint blockade. Sci Transl Med. 2017;9(385):eaak9670.
   PubMed Web of Science ®Google Scholar
• Taylor MH, Rasco DW, Brose MS, et al. A phase 1b/2 trial of lenvatinib plus pembrolizumab in patients with squamous cell carcinoma of the head and neck. J Clin Oncol. 2018;36(15):6016.
   Google Scholar
• Ellington CL, Goodman M, Kono SA, et al. Adenoid cystic carcinoma of the head and neck: incidence and survival trends based on 1973‐2007 surveillance, epidemiology, and end results data. Cancer. 2012;118(18):4444–4451.
   PubMedGoogle Scholar
• Hilberg F, Roth GJ, Krssak M, et al. BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008;68(12):4774–4782.
   PubMed Web of Science ®Google Scholar
• Kim Y, Lee SJ, Lee JY, et al. Clinical trial of nintedanib in patients with recurrent or metastatic salivary gland cancer of the head and neck: A multicenter phase 2 study (korean cancer study group HN14‐01). Cancer. 2017;123(11):1958–1964.
   PubMed Web of Science ®Google Scholar
• Patson B, Cohen RB, Olszanski AJ. Pharmacokinetic evaluation of axitinib. Expert Opin Drug Metab Toxicol. 2012;8(2):259–270.
   PubMed Web of Science ®Google Scholar
• Swiecicki PL, Zhao L, Belile E, et al. A phase II study evaluating axitinib in patients with unresectable, recurrent or metastatic head and neck cancer. Invest New Drugs. 2015;33(6):1248–1256.
   PubMed Web of Science ®Google Scholar
• Faderl S, Talpaz M, Estrov Z, et al. The biology of chronic myeloid leukemia. N Engl J Med. 1999;341(3):164–172.
   PubMed Web of Science ®Google Scholar
• Mino M, Pilch BZ, Faquin WC. Expression of KIT (CD117) in neoplasms of the head and neck: an ancillary marker for adenoid cystic carcinoma. Mod Pathol. 2003;16(12):1224–1231.
   PubMed Web of Science ®Google Scholar
• Hotte SJ, Winquist EW, Lamont E, et al. Imatinib mesylate in patients with adenoid cystic cancers of the salivary glands expressing c-kit: A princess margaret hospital phase II consortium study. J Clin Oncol. 2005;23(3):585–590.
   PubMed Web of Science ®Google Scholar
• Moskaluk CA, Frierson HF, El-Naggar AK, et al. C-kit gene mutations in adenoid cystic carcinoma are rare. Mod Pathol. 2010;23(6):905–906.
   PubMed Web of Science ®Google Scholar
• Weisberg E, Manley PW, Breitenstein W, et al. Characterization of AMN107, a selective inhibitor of native and mutant bcr-abl. Cancer Cell. 2005;7(2):129–141.
   PubMed Web of Science ®Google Scholar
• Saglio G, Kim D, Issaragrisil S, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010;362(24):2251–2259.
   PubMed Web of Science ®Google Scholar
• Kramer B, Hock C, Birk R, et al. Targeted therapies in HPV-positive and-negative HNSCC–alteration of EGFR and VEGFR-2 expression in vitro. Anticancer Res. 2016;36(6):2799–2807.
   PubMed Web of Science ®Google Scholar
• Kramer B, Kneissle M, Birk R, et al. Tyrosine kinase inhibition in HPV-related squamous cell carcinoma reveals beneficial expression of cKIT and src. Anticancer Res. 2018;38(5):2723–2731.
   PubMed Web of Science ®Google Scholar
• Tice DA, Biscardi JS, Nickles AL, et al. Mechanism of biological synergy between cellular src and epidermal growth factor receptor. Proc Nat Acad Sci USA. 1999;96(4):1415–1420.
   PubMed Web of Science ®Google Scholar
• Egloff AM, Grandis JR. Targeting epidermal growth factor receptor and SRC pathways in head and neck cancer. Semin Oncol. 2008;35(3):286–297.
   PubMed Web of Science ®Google Scholar
• Xi S, Zhang Q, Dyer KF, et al. Src kinases mediate STAT growth pathways in squamous cell carcinoma of the head and neck. J Biol Chem. 2003;278(34):31574–31583.
   PubMed Web of Science ®Google Scholar
• Stabile LP, He G, Lui VWY, et al. c-Src activation mediates erlotinib resistance in head and neck cancer by stimulating c-Met. Clin Cancer Res. 2013;19(2):380–392.
   PubMed Web of Science ®Google Scholar
• Bauman JE, Duvvuri U, Gooding WE, et al. Randomized, placebo-controlled window trial of EGFR, Src, or combined blockade in head and neck cancer. JCI Insight. 2017;2(6):e90449.
   PubMed Web of Science ®Google Scholar
• Baro M, De Llobet LI, Figueras A, et al. Dasatinib worsens the effect of cetuximab in combination with fractionated radiotherapy in FaDu-and A431-derived xenografted tumours. Br J Cancer. 2014;111(7):1310–1318.
   PubMed Web of Science ®Google Scholar
• Brooks HD, Glisson BS, Bekele BN, et al. Phase 2 study of dasatinib in the treatment of head and neck squamous cell carcinoma. Cancer. 2011;117(10):2112–2119.
   PubMed Web of Science ®Google Scholar
• Sen B, Saigal B, Parikh N, et al. Sustained src inhibition results in STAT3 activation and cancer cell survival via altered JAK-STAT3 binding. Cancer Res. 2009;69(5):1958–1965.
   PubMed Web of Science ®Google Scholar
• Chen B, Xu X, Luo J, et al. Rapamycin enhances the anti-cancer effect of dasatinib by suppressing src/pi3k/mtor pathway in nsclc cells. PLoS One. 2015;10(6):e0129663.
   PubMed Web of Science ®Google Scholar
• Haltia UM, Andersson N, Yadav B, et al. Systematic drug sensitivity testing reveals synergistic growth inhibition by dasatinib or mtor inhibitors with paclitaxel in ovarian granulosa cell tumor cells. Gynecol Oncol. 2017;144(3):621–630.
   PubMed Web of Science ®Google Scholar
• Lipton JH, Chuah C, Guerci-Bresler A, et al. Ponatinib versus imatinib for newly diagnosed chronic myeloid leukaemia: an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2016;17(5):612–621.
   PubMed Web of Science ®Google Scholar
• Rieke DT, Zuo Z, Endhardt K, et al. Fibroblast growth factors in head and neck cancer: genetic alterations and therapeutic targeting with ponatinib. Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31–Apr 4; Chicago, Illinois. Washington,DC. Philadelphia: AACR; 2012. p. 7.
   Google Scholar
• Cohen EE, Soulières D, Le Tourneau C, et al. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet. 2019;393(10167):156–167.
   PubMed Web of Science ®Google Scholar
• Gillison ML, Trotti AM, Harris J, et al. Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. Lancet. 2019;393(10166):40–50.
   PubMed Web of Science ®Google Scholar
• Stransky N, Egloff AM, Tward AD, et al. The mutational landscape of head and neck squamous cell carcinoma. Science. 2011;333(6046):1157–1160.
   PubMed Web of Science ®Google Scholar
• Cancer Genome Atlas Network. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015;517(7536):576–582.
   PubMed Web of Science ®Google Scholar