Personalizing Medicine in Head and Neck Squamous Cell Carcinoma: The Rationale for Combination Therapies
Main Article Content
Abstract
Abstract
Personalized medicine, in which individual tumor genetics drive the selection of targeted therapies and treatment plans for each patient, has recently emerged as the next generation of cancer therapy. Unfortunately, personalized medicine trials have had limited success in tumors that have complex combinations of disruptive genomic events, which drive differential responses to targeted therapies. Here, we will use head and neck squamous cell carcinoma as a model for genetically complex disease and discuss novel approaches to enhance personalized medicine trials for these complicated cases.
Article Details
How to Cite
BRENNER, Chad; BIRKELAND, Andrew C..
Personalizing Medicine in Head and Neck Squamous Cell Carcinoma: The Rationale for Combination Therapies.
Medical Research Archives, [S.l.], n. 3, apr. 2015.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/77>. Date accessed: 19 apr. 2024.
Keywords
HNSCC, Personalized Medicine, Sequencing
Issue
Section
Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
Agrawal N, Frederick MJ, Pickering CR et al. Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science. 2011; 333(6046): 1154-7.
Ang KK, Harris J, Wheeler R et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010; 363(1):24-35.
Argiris A, Ghebremichael M, Gilbert J et al. Phase III randomized, placebo-controlled trial of docetaxel with or without gefitinib in recurrent or metastatic head and neck cancer: an eastern cooperative oncology group trial. J Clin Oncol. 2013; 31(11): 1405-14.
Asangani IA, Dommeti VL, Wang X et al. Therapeutic targeting of BET bromodomain proteins in castration-resistant prostate cancer. Nature. 2014; 510(7504): 278-82.
Bean J, Brennan C, Shih JY et al. MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Natl Acad Sci U S A. 2007; 104(52):20392-7.
Benvenuti S, Sartore-Bianchi A, Di Nicolantonio F et al. Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res. 2007; 67(6):2643-8.
Birkeland AC, Uhlmann WR, Brenner JC, Shuman AG. Getting personal: Head and neck cancer management in the era of personalized medicine. Manuscript in review.
Birkeland AC, Yanik M, Tillman BN et al. Identification of HER2 amplifications in head and neck squamous cell carcinoma. Manuscript in review.
Bonner JA, Harari PM, Giralt J et al. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010; 11(1): 21-8.
Bookman MA, Darcy KM, Clarke-Pearson D et al. Evaluation of monoclonal humanized anti-HER2 antibody, trastuzumab, in patients with recurrent or refractory ovarian or primary peritoneal carcinoma with overexpression of HER2; a phase II trial of the Gynecologic Oncology Group. J Clin Oncol. 2003; 21(2): 283-90.
Brenner JC, Ateeq B, Li Y et al. Mechanistic rationale for inhibition of poly(ADP-ribose) polymerase in ETS gene fusion-positive prostate cancer. Cancer Cell. 2011; 19(5): 664-78.
Cancer Genome Atlas Network. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015; 517(7536): 576-82.
Cappuzzo F, Ciuleanu T, Stehlmakh L et al. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2010; 11(6): 521-9.
Chaturvedi AK, Engels EA, Anderson WF, Gillison ML. Incidence trends for human papillomavirus-related and –unrelated oral squamous cell carcinomas in the United States. J Clin Oncol. 2008; 26(4):612-9.
Chen D, Frezza M, Schmitt S, Kanwar J, Dou QP. Bortezomib as the first proteasome inhibitor anticancer drug: current status and future perspectives. Curr Cancer Drug Targets. 2011; 11(3):239-53.
Conley BA, Doroshow JH. Molecular analysis for therapy choice: NCI MATCH. Semin Oncol. 2014; 41(3):297-9.
D’Amato V, Rosa R, D’Amato C et al. The dual PI3K/mTOR inhibitor PKI-587 enhances sensitivity to cetuximab in EGFR-resistant human head and neck cancer models. Br J Cancer. 2014; 110(12): 2887-95.
Druker BJ, Guilhot F, O’Brien SG et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006; 355(23): 2408-17.
Everett JN, Gustafson SL, Raymond VM. Traditional roles in non-traditional setting: genetic counseling in precision oncology. J Genet Couns. 2014; 23(4): 655-60.
Finn RS, Crown JP, Lang I et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as a first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015; 16(1):25-35.
Fisher R, Pusztai L, Swanton C. Cancer heterogeneity: implications for targeted therapeutics. Br J Cancer. 2013; 108(3): 479-85.
Flaherty KT, Puzanov I, Kim KB et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med. 2010; 363(9): 809-19.
Geyer CE, Forster J, Lindquist et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006; 355(26):2733-43.
Givens DJ, Karnell LH, Gupta AK et al. Adverse events associated with concurrent chemoradiation therapy in patients with head and neck cancer. Arch Otolaryngol Head Neck Surg. 2009; 135(12):1209-17.
Goke F, Bode M, Franzen A et al. Fibroblast growth factor receptor 1 amplification is a common event in squamous cell carcinoma of the head and neck. Mod Pathol. 2013; 26(10): 1298-306.
Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000; 100(1):57-70.
Imai A, Zeitlin BD, Visoli F et al. Metronomic dosing of BH3 mimetic small molecule yields robust antiangiogenic and antitumor effects. Cancer Res. 2012; 72(3):716-25.
Janjigian YY, Smit EF, Groen HJ et al. Dual inhibition with afatinib and cetuximab in kinase inhibitor-resistant EGFR-mutant lung cancer with and without T790M mutations. Cancer Discov. 2014; 4(9):1036-45.
Janne PA, Gray N, Settleman J. Factors underlying sensitivity of cancers to small-molecule kinase inhibitors. Nat Rev Drug Discov. 2009; 8(9):709-23.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011; 61(2):69-90.
Kobayashi S, Boggon TJ, Dayaram T et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med. 2005; 352(8):786-92.
Li H, Wawrose JS, Gooding WE et al. Genomic analysis of head and neck squamous cell carcinoma cell lines and human tumors: a rational approach to preclinical model selection. Mol Cancer Res. 2014; 12(4): 571-82.
Li P, Conley A, Zhang H, Kim HL. Whole-transcriptome profiling of formalin-fixed, paraffin-embedded renal cell carcinoma by RNA-seq. BMC Genomics. 2014; 15(1): 1087.
Lievre A, Bachet JB, Le Corre D et al. KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res. 2006; 66(8):3992-5.
Liu J, Pan S, Hsieh MH et al. Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974. Proc Natl Acad Sci U S A. 2013; 110(50):20224-9.
Liu S, Chen P, Hu M et al. Randomized, controlled phase II study of post-surgery radiotherapy combined with recombinant human p53 gene therapy in treatment of oral cancer. Cancer Gene Ther. 2013; 20(6):375-8.
Pickering CR, Zhang J, Yoo SY et al. Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers. Cancer Discov. 2013; 3(7): 770-81.
Pollock NI, Grandis JR. HER2 as a therapeutic target in head and neck squamous cell carcinoma. Clin Cancer Res. 2014; epub.
Pulte D, Brenner H. Changes in survival in head and neck cancers in the late 20th and early 21st century: a period analysis. Oncologist. 2010; 15(9): 994-1001.
Qin JZ, Ziffra J, Stennett L et al. Proteasome inhibitors trigger NOXA-mediated apoptosis in melanoma and myeloma cells. Cancer Res. 2005; 65(14):6282-93.
Rhodes DR, Yu J, Shanker K et al. ONCOMINE: a cancer microarray database and integrated data-mining platform. Neoplasia. 2004; 6(1): 1-6.
Ribas A, Hodi FS, Callahan M, Konto C, Wolchok J. Hepatotoxicity with combination of vemurafenib and ipilimumab. N Engl J Med. 2013; 368(14):1365-6.
Robert C, Long GV, Brady B et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015; 372(4):320-30.
Robert C, Thomas L, Bondarenko I et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011; 364(26):2517-26.
Robinson DR, YM, Vats P et al. Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet. 2013; 45(12): 1446-51.
Roychowdhury S, Chinnaiyan AM. Translating genomics for precision cancer medicine. Annu Rev Genomics Hum Genet. 2014; 15: 395-415.
Roychowdhury S, Iyer MK, Robinson DR et al. Personalized oncology through integrative high-throughput sequencing: a pilot study. Sci Transl Med. 2011; 3(111): 111-21.
Ryan CJ, Smith MR, de Bono JS et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013; 368(2): 138-48.
Saltz LB, Clarke S, Diaz-Rubio E et al. Bevacizumab in combination with oxaplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomised phase III study. J Clin Oncol. 2008; 26(12): 2013-9.
Sekulic A, Migden MR, Oro AE et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med. 2012; 366(23):2171-9.
Shalem O, Sanjana NE, Hartenian E et al. Genome-scale CRISPR-Cas9 knockout screening in human cells. Science. 2014; 343(6166): 84-87.
Shtivelman E, Lifshitz B, Gale RP, Canaani E. Fused transcript of abl and bcr genes in chronic myelogenous leukemia. Nature. 1985; 315(6020): 550-4.
Simpson DR, Mell LK, Cohen EE. Targeting the PI3K/AKT/mTOR pathway in squamous cell carcinoma of the head and neck. Oral Oncol. 2014; epub.
Slamon DJ, Leyland-Jones B, Shak S et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001; 344(11): 783-92.
Stahel R, Bogaerts J, Ciardiello F et al. Optimising translational oncology in clinical practice: Strategies to accelerate progress in drug development. Cancer Treat Rev. 2014; epub.
Stransky N, Egloff AM, Tward AD et al. The mutational landscape of head and neck squamous cell carcinoma. Science. 2011; 333(6046): 1157-60.
Swain SM, Baselga J, Kim SB et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015; 372(8):724-34.
Takezawa K, Pirazzoli V, Arcila ME et al. HER2 amplification: a potential mechanism of acquired resistance to EGFR inhibition in EGFR-mutant lung cancers that lack the second-site EGFRT790M mutation. Cancer Discov. 2012; 2(10):922-33.
Tijink BM, Buter J, de Bree R et al. A phase I dose escalation study with anti-CD44v6 bivatuzumab mertansine in patients with incurable squamous cell carcinoma of the head and neck or esophagus. Clin Cancer Res. 2006; 12(20 Pt 1):6064-72.
Tillman BN et al. Targeted sequencing of an epidemiologically low risk patient defines fibroblast growth factor family aberrations as a driver of head and neck squamous cell carcinoma. Manuscript in review.
Van Cutsem E, Kohne CH, Lang I et al. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 2011; 29(15): 2011-9.
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): 1116-27.
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 who failed to respond to platinum-based therapy. L Clin Oncol. 2007; 25(16):2171-7.
Wang T, Wei JJ, Sabatini DM, Lander ES. Genetic screens in human cells using the CRISPR-Cas9 system. Science. 2014; 343(6166): 80-84.
Wang Z, Martin D, Molinolo AA et al. mTor co-targeting in cetuximab resistance in head and neck cancers harboring PIK3CA and RAS mutations. J Natl Cancer Inst. 2014; 106(9).
Ang KK, Harris J, Wheeler R et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010; 363(1):24-35.
Argiris A, Ghebremichael M, Gilbert J et al. Phase III randomized, placebo-controlled trial of docetaxel with or without gefitinib in recurrent or metastatic head and neck cancer: an eastern cooperative oncology group trial. J Clin Oncol. 2013; 31(11): 1405-14.
Asangani IA, Dommeti VL, Wang X et al. Therapeutic targeting of BET bromodomain proteins in castration-resistant prostate cancer. Nature. 2014; 510(7504): 278-82.
Bean J, Brennan C, Shih JY et al. MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Natl Acad Sci U S A. 2007; 104(52):20392-7.
Benvenuti S, Sartore-Bianchi A, Di Nicolantonio F et al. Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res. 2007; 67(6):2643-8.
Birkeland AC, Uhlmann WR, Brenner JC, Shuman AG. Getting personal: Head and neck cancer management in the era of personalized medicine. Manuscript in review.
Birkeland AC, Yanik M, Tillman BN et al. Identification of HER2 amplifications in head and neck squamous cell carcinoma. Manuscript in review.
Bonner JA, Harari PM, Giralt J et al. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010; 11(1): 21-8.
Bookman MA, Darcy KM, Clarke-Pearson D et al. Evaluation of monoclonal humanized anti-HER2 antibody, trastuzumab, in patients with recurrent or refractory ovarian or primary peritoneal carcinoma with overexpression of HER2; a phase II trial of the Gynecologic Oncology Group. J Clin Oncol. 2003; 21(2): 283-90.
Brenner JC, Ateeq B, Li Y et al. Mechanistic rationale for inhibition of poly(ADP-ribose) polymerase in ETS gene fusion-positive prostate cancer. Cancer Cell. 2011; 19(5): 664-78.
Cancer Genome Atlas Network. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015; 517(7536): 576-82.
Cappuzzo F, Ciuleanu T, Stehlmakh L et al. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2010; 11(6): 521-9.
Chaturvedi AK, Engels EA, Anderson WF, Gillison ML. Incidence trends for human papillomavirus-related and –unrelated oral squamous cell carcinomas in the United States. J Clin Oncol. 2008; 26(4):612-9.
Chen D, Frezza M, Schmitt S, Kanwar J, Dou QP. Bortezomib as the first proteasome inhibitor anticancer drug: current status and future perspectives. Curr Cancer Drug Targets. 2011; 11(3):239-53.
Conley BA, Doroshow JH. Molecular analysis for therapy choice: NCI MATCH. Semin Oncol. 2014; 41(3):297-9.
D’Amato V, Rosa R, D’Amato C et al. The dual PI3K/mTOR inhibitor PKI-587 enhances sensitivity to cetuximab in EGFR-resistant human head and neck cancer models. Br J Cancer. 2014; 110(12): 2887-95.
Druker BJ, Guilhot F, O’Brien SG et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006; 355(23): 2408-17.
Everett JN, Gustafson SL, Raymond VM. Traditional roles in non-traditional setting: genetic counseling in precision oncology. J Genet Couns. 2014; 23(4): 655-60.
Finn RS, Crown JP, Lang I et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as a first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015; 16(1):25-35.
Fisher R, Pusztai L, Swanton C. Cancer heterogeneity: implications for targeted therapeutics. Br J Cancer. 2013; 108(3): 479-85.
Flaherty KT, Puzanov I, Kim KB et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med. 2010; 363(9): 809-19.
Geyer CE, Forster J, Lindquist et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006; 355(26):2733-43.
Givens DJ, Karnell LH, Gupta AK et al. Adverse events associated with concurrent chemoradiation therapy in patients with head and neck cancer. Arch Otolaryngol Head Neck Surg. 2009; 135(12):1209-17.
Goke F, Bode M, Franzen A et al. Fibroblast growth factor receptor 1 amplification is a common event in squamous cell carcinoma of the head and neck. Mod Pathol. 2013; 26(10): 1298-306.
Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000; 100(1):57-70.
Imai A, Zeitlin BD, Visoli F et al. Metronomic dosing of BH3 mimetic small molecule yields robust antiangiogenic and antitumor effects. Cancer Res. 2012; 72(3):716-25.
Janjigian YY, Smit EF, Groen HJ et al. Dual inhibition with afatinib and cetuximab in kinase inhibitor-resistant EGFR-mutant lung cancer with and without T790M mutations. Cancer Discov. 2014; 4(9):1036-45.
Janne PA, Gray N, Settleman J. Factors underlying sensitivity of cancers to small-molecule kinase inhibitors. Nat Rev Drug Discov. 2009; 8(9):709-23.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011; 61(2):69-90.
Kobayashi S, Boggon TJ, Dayaram T et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med. 2005; 352(8):786-92.
Li H, Wawrose JS, Gooding WE et al. Genomic analysis of head and neck squamous cell carcinoma cell lines and human tumors: a rational approach to preclinical model selection. Mol Cancer Res. 2014; 12(4): 571-82.
Li P, Conley A, Zhang H, Kim HL. Whole-transcriptome profiling of formalin-fixed, paraffin-embedded renal cell carcinoma by RNA-seq. BMC Genomics. 2014; 15(1): 1087.
Lievre A, Bachet JB, Le Corre D et al. KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res. 2006; 66(8):3992-5.
Liu J, Pan S, Hsieh MH et al. Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974. Proc Natl Acad Sci U S A. 2013; 110(50):20224-9.
Liu S, Chen P, Hu M et al. Randomized, controlled phase II study of post-surgery radiotherapy combined with recombinant human p53 gene therapy in treatment of oral cancer. Cancer Gene Ther. 2013; 20(6):375-8.
Pickering CR, Zhang J, Yoo SY et al. Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers. Cancer Discov. 2013; 3(7): 770-81.
Pollock NI, Grandis JR. HER2 as a therapeutic target in head and neck squamous cell carcinoma. Clin Cancer Res. 2014; epub.
Pulte D, Brenner H. Changes in survival in head and neck cancers in the late 20th and early 21st century: a period analysis. Oncologist. 2010; 15(9): 994-1001.
Qin JZ, Ziffra J, Stennett L et al. Proteasome inhibitors trigger NOXA-mediated apoptosis in melanoma and myeloma cells. Cancer Res. 2005; 65(14):6282-93.
Rhodes DR, Yu J, Shanker K et al. ONCOMINE: a cancer microarray database and integrated data-mining platform. Neoplasia. 2004; 6(1): 1-6.
Ribas A, Hodi FS, Callahan M, Konto C, Wolchok J. Hepatotoxicity with combination of vemurafenib and ipilimumab. N Engl J Med. 2013; 368(14):1365-6.
Robert C, Long GV, Brady B et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015; 372(4):320-30.
Robert C, Thomas L, Bondarenko I et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011; 364(26):2517-26.
Robinson DR, YM, Vats P et al. Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet. 2013; 45(12): 1446-51.
Roychowdhury S, Chinnaiyan AM. Translating genomics for precision cancer medicine. Annu Rev Genomics Hum Genet. 2014; 15: 395-415.
Roychowdhury S, Iyer MK, Robinson DR et al. Personalized oncology through integrative high-throughput sequencing: a pilot study. Sci Transl Med. 2011; 3(111): 111-21.
Ryan CJ, Smith MR, de Bono JS et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013; 368(2): 138-48.
Saltz LB, Clarke S, Diaz-Rubio E et al. Bevacizumab in combination with oxaplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomised phase III study. J Clin Oncol. 2008; 26(12): 2013-9.
Sekulic A, Migden MR, Oro AE et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med. 2012; 366(23):2171-9.
Shalem O, Sanjana NE, Hartenian E et al. Genome-scale CRISPR-Cas9 knockout screening in human cells. Science. 2014; 343(6166): 84-87.
Shtivelman E, Lifshitz B, Gale RP, Canaani E. Fused transcript of abl and bcr genes in chronic myelogenous leukemia. Nature. 1985; 315(6020): 550-4.
Simpson DR, Mell LK, Cohen EE. Targeting the PI3K/AKT/mTOR pathway in squamous cell carcinoma of the head and neck. Oral Oncol. 2014; epub.
Slamon DJ, Leyland-Jones B, Shak S et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001; 344(11): 783-92.
Stahel R, Bogaerts J, Ciardiello F et al. Optimising translational oncology in clinical practice: Strategies to accelerate progress in drug development. Cancer Treat Rev. 2014; epub.
Stransky N, Egloff AM, Tward AD et al. The mutational landscape of head and neck squamous cell carcinoma. Science. 2011; 333(6046): 1157-60.
Swain SM, Baselga J, Kim SB et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015; 372(8):724-34.
Takezawa K, Pirazzoli V, Arcila ME et al. HER2 amplification: a potential mechanism of acquired resistance to EGFR inhibition in EGFR-mutant lung cancers that lack the second-site EGFRT790M mutation. Cancer Discov. 2012; 2(10):922-33.
Tijink BM, Buter J, de Bree R et al. A phase I dose escalation study with anti-CD44v6 bivatuzumab mertansine in patients with incurable squamous cell carcinoma of the head and neck or esophagus. Clin Cancer Res. 2006; 12(20 Pt 1):6064-72.
Tillman BN et al. Targeted sequencing of an epidemiologically low risk patient defines fibroblast growth factor family aberrations as a driver of head and neck squamous cell carcinoma. Manuscript in review.
Van Cutsem E, Kohne CH, Lang I et al. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 2011; 29(15): 2011-9.
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): 1116-27.
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 who failed to respond to platinum-based therapy. L Clin Oncol. 2007; 25(16):2171-7.
Wang T, Wei JJ, Sabatini DM, Lander ES. Genetic screens in human cells using the CRISPR-Cas9 system. Science. 2014; 343(6166): 80-84.
Wang Z, Martin D, Molinolo AA et al. mTor co-targeting in cetuximab resistance in head and neck cancers harboring PIK3CA and RAS mutations. J Natl Cancer Inst. 2014; 106(9).