title: Clinical Utility of Patient-Derived Xenografts to Determine Biomarkers of Prognosis and Map Resistance Pathways in EGFR-Mutant Lung Adenocarcinoma.
abstract: OBJECTIVE
  Although epidermal growth factor receptor (EGFR) -mutated adenocarcinomas initially have high response rates to EGFR tyrosine kinase inhibitors (TKIs), most patients eventually develop resistance. Patient-derived xenografts (PDXs) are considered preferred preclinical models to study the biology of patient tumors. EGFR-mutant PDX models may be valuable tools to study the biology of these tumors and to elucidate mechanisms of resistance to EGFR-targeted therapies.
  
  
  METHODS
  Surgically resected early-stage non-small-cell lung carcinoma (NSCLC) tumors were implanted into nonobese diabetic severe combined immune deficient (NOD-SCID) mice. EGFR TKI treatment was initiated at tumor volumes of 150 μL. Gene expression analysis was performed using a microarray platform.
  
  
  RESULTS
  Of 33 lung adenocarcinomas with EGFR activating mutations, only 6 (18%) engrafted and could be propagated beyond passage one. Engraftment was associated with upregulation of genes involved in mitotic checkpoint and cell proliferation. A differentially expressed gene set between engrafting and nonengrafting patients could identify patients harboring EGFR-mutant tumor with significantly different prognoses in The Cancer Genome Atlas Lung Adenocarcinoma datasets. The PDXs included models with variable sensitivity to first- and second-generation EGFR TKIs and the monoclonal antibody cetuximab. All EGFR-mutant NSCLC PDXs studied closely recapitulated their corresponding patient tumor phenotype and clinical course, including response pattern to EGFR TKIs.
  
  
  CONCLUSIONS
  PDX models closely recapitulate primary tumor biology and clinical outcome. They may serve as important laboratory models to investigate mechanisms of resistance to targeted therapies, and for preclinical testing of novel treatment strategies.
authors.affiliation: Erin L. Stewart, Celine Mascaux, Nhu-An Pham, Shingo Sakashita, Jenna Sykes, Lucia Kim, Naoki Yanagawa, Ghassan Allo, Kota Ishizawa, Dennis Wang, Chang-Qi Zhu, Ming Li, Christine Ng, Ni Liu, Melania Pintilie, Petra Martin, Tom John, Igor Jurisica, Natasha B. Leighl, Benjamin G. Neel, Thomas K. Waddell, Frances A. Shepherd, Geoffrey Liu, Ming-Sound Tsao, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; Lucia Kim, Inha University College of Medicine, Incheon, South Korea; and Tom John, Austin Hospital, Heidelberg, Australia.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Stewart
authors.affiliation: Erin L. Stewart, Celine Mascaux, Nhu-An Pham, Shingo Sakashita, Jenna Sykes, Lucia Kim, Naoki Yanagawa, Ghassan Allo, Kota Ishizawa, Dennis Wang, Chang-Qi Zhu, Ming Li, Christine Ng, Ni Liu, Melania Pintilie, Petra Martin, Tom John, Igor Jurisica, Natasha B. Leighl, Benjamin G. Neel, Thomas K. Waddell, Frances A. Shepherd, Geoffrey Liu, Ming-Sound Tsao, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; Lucia Kim, Inha University College of Medicine, Incheon, South Korea; and Tom John, Austin Hospital, Heidelberg, Australia.
authors.forename: Celine
authors.initials: C
authors.lastname: Mascaux
authors.affiliation: Erin L. Stewart, Celine Mascaux, Nhu-An Pham, Shingo Sakashita, Jenna Sykes, Lucia Kim, Naoki Yanagawa, Ghassan Allo, Kota Ishizawa, Dennis Wang, Chang-Qi Zhu, Ming Li, Christine Ng, Ni Liu, Melania Pintilie, Petra Martin, Tom John, Igor Jurisica, Natasha B. Leighl, Benjamin G. Neel, Thomas K. Waddell, Frances A. Shepherd, Geoffrey Liu, Ming-Sound Tsao, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; Lucia Kim, Inha University College of Medicine, Incheon, South Korea; and Tom John, Austin Hospital, Heidelberg, Australia.
authors.forename: Nhu-An
authors.initials: NA
authors.lastname: Pham
authors.affiliation: Erin L. Stewart, Celine Mascaux, Nhu-An Pham, Shingo Sakashita, Jenna Sykes, Lucia Kim, Naoki Yanagawa, Ghassan Allo, Kota Ishizawa, Dennis Wang, Chang-Qi Zhu, Ming Li, Christine Ng, Ni Liu, Melania Pintilie, Petra Martin, Tom John, Igor Jurisica, Natasha B. Leighl, Benjamin G. Neel, Thomas K. Waddell, Frances A. Shepherd, Geoffrey Liu, Ming-Sound Tsao, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; Lucia Kim, Inha University College of Medicine, Incheon, South Korea; and Tom John, Austin Hospital, Heidelberg, Australia.
authors.forename: Shingo
authors.initials: S
authors.lastname: Sakashita
authors.affiliation: Erin L. Stewart, Celine Mascaux, Nhu-An Pham, Shingo Sakashita, Jenna Sykes, Lucia Kim, Naoki Yanagawa, Ghassan Allo, Kota Ishizawa, Dennis Wang, Chang-Qi Zhu, Ming Li, Christine Ng, Ni Liu, Melania Pintilie, Petra Martin, Tom John, Igor Jurisica, Natasha B. Leighl, Benjamin G. Neel, Thomas K. Waddell, Frances A. Shepherd, Geoffrey Liu, Ming-Sound Tsao, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; Lucia Kim, Inha University College of Medicine, Incheon, South Korea; and Tom John, Austin Hospital, Heidelberg, Australia.
authors.forename: Jenna
authors.initials: J
authors.lastname: Sykes
authors.affiliation: Erin L. Stewart, Celine Mascaux, Nhu-An Pham, Shingo Sakashita, Jenna Sykes, Lucia Kim, Naoki Yanagawa, Ghassan Allo, Kota Ishizawa, Dennis Wang, Chang-Qi Zhu, Ming Li, Christine Ng, Ni Liu, Melania Pintilie, Petra Martin, Tom John, Igor Jurisica, Natasha B. Leighl, Benjamin G. Neel, Thomas K. Waddell, Frances A. Shepherd, Geoffrey Liu, Ming-Sound Tsao, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; Lucia Kim, Inha University College of Medicine, Incheon, South Korea; and Tom John, Austin Hospital, Heidelberg, Australia.
authors.forename: Lucia
authors.initials: L
authors.lastname: Kim
authors.affiliation: Erin L. Stewart, Celine Mascaux, Nhu-An Pham, Shingo Sakashita, Jenna Sykes, Lucia Kim, Naoki Yanagawa, Ghassan Allo, Kota Ishizawa, Dennis Wang, Chang-Qi Zhu, Ming Li, Christine Ng, Ni Liu, Melania Pintilie, Petra Martin, Tom John, Igor Jurisica, Natasha B. Leighl, Benjamin G. Neel, Thomas K. Waddell, Frances A. Shepherd, Geoffrey Liu, Ming-Sound Tsao, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; Lucia Kim, Inha University College of Medicine, Incheon, South Korea; and Tom John, Austin Hospital, Heidelberg, Australia.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yanagawa
authors.affiliation: Erin L. Stewart, Celine Mascaux, Nhu-An Pham, Shingo Sakashita, Jenna Sykes, Lucia Kim, Naoki Yanagawa, Ghassan Allo, Kota Ishizawa, Dennis Wang, Chang-Qi Zhu, Ming Li, Christine Ng, Ni Liu, Melania Pintilie, Petra Martin, Tom John, Igor Jurisica, Natasha B. Leighl, Benjamin G. Neel, Thomas K. Waddell, Frances A. Shepherd, Geoffrey Liu, Ming-Sound Tsao, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; Lucia Kim, Inha University College of Medicine, Incheon, South Korea; and Tom John, Austin Hospital, Heidelberg, Australia.
authors.forename: Ghassan
authors.initials: G
authors.lastname: Allo
authors.affiliation: Erin L. Stewart, Celine Mascaux, Nhu-An Pham, Shingo Sakashita, Jenna Sykes, Lucia Kim, Naoki Yanagawa, Ghassan Allo, Kota Ishizawa, Dennis Wang, Chang-Qi Zhu, Ming Li, Christine Ng, Ni Liu, Melania Pintilie, Petra Martin, Tom John, Igor Jurisica, Natasha B. Leighl, Benjamin G. Neel, Thomas K. Waddell, Frances A. Shepherd, Geoffrey Liu, Ming-Sound Tsao, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; Lucia Kim, Inha University College of Medicine, Incheon, South Korea; and Tom John, Austin Hospital, Heidelberg, Australia.
authors.forename: Kota
authors.initials: K
authors.lastname: Ishizawa
authors.affiliation: Erin L. Stewart, Celine Mascaux, Nhu-An Pham, Shingo Sakashita, Jenna Sykes, Lucia Kim, Naoki Yanagawa, Ghassan Allo, Kota Ishizawa, Dennis Wang, Chang-Qi Zhu, Ming Li, Christine Ng, Ni Liu, Melania Pintilie, Petra Martin, Tom John, Igor Jurisica, Natasha B. Leighl, Benjamin G. Neel, Thomas K. Waddell, Frances A. Shepherd, Geoffrey Liu, Ming-Sound Tsao, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; Lucia Kim, Inha University College of Medicine, Incheon, South Korea; and Tom John, Austin Hospital, Heidelberg, Australia.
authors.forename: Dennis
authors.initials: D
authors.lastname: Wang
authors.affiliation: Erin L. Stewart, Celine Mascaux, Nhu-An Pham, Shingo Sakashita, Jenna Sykes, Lucia Kim, Naoki Yanagawa, Ghassan Allo, Kota Ishizawa, Dennis Wang, Chang-Qi Zhu, Ming Li, Christine Ng, Ni Liu, Melania Pintilie, Petra Martin, Tom John, Igor Jurisica, Natasha B. Leighl, Benjamin G. Neel, Thomas K. Waddell, Frances A. Shepherd, Geoffrey Liu, Ming-Sound Tsao, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; Lucia Kim, Inha University College of Medicine, Incheon, South Korea; and Tom John, Austin Hospital, Heidelberg, Australia.
authors.forename: Chang-Qi
authors.initials: CQ
authors.lastname: Zhu
authors.affiliation: Erin L. Stewart, Celine Mascaux, Nhu-An Pham, Shingo Sakashita, Jenna Sykes, Lucia Kim, Naoki Yanagawa, Ghassan Allo, Kota Ishizawa, Dennis Wang, Chang-Qi Zhu, Ming Li, Christine Ng, Ni Liu, Melania Pintilie, Petra Martin, Tom John, Igor Jurisica, Natasha B. Leighl, Benjamin G. Neel, Thomas K. Waddell, Frances A. Shepherd, Geoffrey Liu, Ming-Sound Tsao, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; Lucia Kim, Inha University College of Medicine, Incheon, South Korea; and Tom John, Austin Hospital, Heidelberg, Australia.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Erin L. Stewart, Celine Mascaux, Nhu-An Pham, Shingo Sakashita, Jenna Sykes, Lucia Kim, Naoki Yanagawa, Ghassan Allo, Kota Ishizawa, Dennis Wang, Chang-Qi Zhu, Ming Li, Christine Ng, Ni Liu, Melania Pintilie, Petra Martin, Tom John, Igor Jurisica, Natasha B. Leighl, Benjamin G. Neel, Thomas K. Waddell, Frances A. Shepherd, Geoffrey Liu, Ming-Sound Tsao, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; Lucia Kim, Inha University College of Medicine, Incheon, South Korea; and Tom John, Austin Hospital, Heidelberg, Australia.
authors.forename: Christine
authors.initials: C
authors.lastname: Ng
authors.affiliation: Erin L. Stewart, Celine Mascaux, Nhu-An Pham, Shingo Sakashita, Jenna Sykes, Lucia Kim, Naoki Yanagawa, Ghassan Allo, Kota Ishizawa, Dennis Wang, Chang-Qi Zhu, Ming Li, Christine Ng, Ni Liu, Melania Pintilie, Petra Martin, Tom John, Igor Jurisica, Natasha B. Leighl, Benjamin G. Neel, Thomas K. Waddell, Frances A. Shepherd, Geoffrey Liu, Ming-Sound Tsao, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; Lucia Kim, Inha University College of Medicine, Incheon, South Korea; and Tom John, Austin Hospital, Heidelberg, Australia.
authors.forename: Ni
authors.initials: N
authors.lastname: Liu
authors.affiliation: Erin L. Stewart, Celine Mascaux, Nhu-An Pham, Shingo Sakashita, Jenna Sykes, Lucia Kim, Naoki Yanagawa, Ghassan Allo, Kota Ishizawa, Dennis Wang, Chang-Qi Zhu, Ming Li, Christine Ng, Ni Liu, Melania Pintilie, Petra Martin, Tom John, Igor Jurisica, Natasha B. Leighl, Benjamin G. Neel, Thomas K. Waddell, Frances A. Shepherd, Geoffrey Liu, Ming-Sound Tsao, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; Lucia Kim, Inha University College of Medicine, Incheon, South Korea; and Tom John, Austin Hospital, Heidelberg, Australia.
authors.forename: Melania
authors.initials: M
authors.lastname: Pintilie
authors.affiliation: Erin L. Stewart, Celine Mascaux, Nhu-An Pham, Shingo Sakashita, Jenna Sykes, Lucia Kim, Naoki Yanagawa, Ghassan Allo, Kota Ishizawa, Dennis Wang, Chang-Qi Zhu, Ming Li, Christine Ng, Ni Liu, Melania Pintilie, Petra Martin, Tom John, Igor Jurisica, Natasha B. Leighl, Benjamin G. Neel, Thomas K. Waddell, Frances A. Shepherd, Geoffrey Liu, Ming-Sound Tsao, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; Lucia Kim, Inha University College of Medicine, Incheon, South Korea; and Tom John, Austin Hospital, Heidelberg, Australia.
authors.forename: Petra
authors.initials: P
authors.lastname: Martin
authors.affiliation: Erin L. Stewart, Celine Mascaux, Nhu-An Pham, Shingo Sakashita, Jenna Sykes, Lucia Kim, Naoki Yanagawa, Ghassan Allo, Kota Ishizawa, Dennis Wang, Chang-Qi Zhu, Ming Li, Christine Ng, Ni Liu, Melania Pintilie, Petra Martin, Tom John, Igor Jurisica, Natasha B. Leighl, Benjamin G. Neel, Thomas K. Waddell, Frances A. Shepherd, Geoffrey Liu, Ming-Sound Tsao, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; Lucia Kim, Inha University College of Medicine, Incheon, South Korea; and Tom John, Austin Hospital, Heidelberg, Australia.
authors.forename: Tom
authors.initials: T
authors.lastname: John
authors.affiliation: Erin L. Stewart, Celine Mascaux, Nhu-An Pham, Shingo Sakashita, Jenna Sykes, Lucia Kim, Naoki Yanagawa, Ghassan Allo, Kota Ishizawa, Dennis Wang, Chang-Qi Zhu, Ming Li, Christine Ng, Ni Liu, Melania Pintilie, Petra Martin, Tom John, Igor Jurisica, Natasha B. Leighl, Benjamin G. Neel, Thomas K. Waddell, Frances A. Shepherd, Geoffrey Liu, Ming-Sound Tsao, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; Lucia Kim, Inha University College of Medicine, Incheon, South Korea; and Tom John, Austin Hospital, Heidelberg, Australia.
authors.forename: Igor
authors.initials: I
authors.lastname: Jurisica
authors.affiliation: Erin L. Stewart, Celine Mascaux, Nhu-An Pham, Shingo Sakashita, Jenna Sykes, Lucia Kim, Naoki Yanagawa, Ghassan Allo, Kota Ishizawa, Dennis Wang, Chang-Qi Zhu, Ming Li, Christine Ng, Ni Liu, Melania Pintilie, Petra Martin, Tom John, Igor Jurisica, Natasha B. Leighl, Benjamin G. Neel, Thomas K. Waddell, Frances A. Shepherd, Geoffrey Liu, Ming-Sound Tsao, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; Lucia Kim, Inha University College of Medicine, Incheon, South Korea; and Tom John, Austin Hospital, Heidelberg, Australia.
authors.forename: Natasha B
authors.initials: NB
authors.lastname: Leighl
authors.affiliation: Erin L. Stewart, Celine Mascaux, Nhu-An Pham, Shingo Sakashita, Jenna Sykes, Lucia Kim, Naoki Yanagawa, Ghassan Allo, Kota Ishizawa, Dennis Wang, Chang-Qi Zhu, Ming Li, Christine Ng, Ni Liu, Melania Pintilie, Petra Martin, Tom John, Igor Jurisica, Natasha B. Leighl, Benjamin G. Neel, Thomas K. Waddell, Frances A. Shepherd, Geoffrey Liu, Ming-Sound Tsao, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; Lucia Kim, Inha University College of Medicine, Incheon, South Korea; and Tom John, Austin Hospital, Heidelberg, Australia.
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Neel
authors.affiliation: Erin L. Stewart, Celine Mascaux, Nhu-An Pham, Shingo Sakashita, Jenna Sykes, Lucia Kim, Naoki Yanagawa, Ghassan Allo, Kota Ishizawa, Dennis Wang, Chang-Qi Zhu, Ming Li, Christine Ng, Ni Liu, Melania Pintilie, Petra Martin, Tom John, Igor Jurisica, Natasha B. Leighl, Benjamin G. Neel, Thomas K. Waddell, Frances A. Shepherd, Geoffrey Liu, Ming-Sound Tsao, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; Lucia Kim, Inha University College of Medicine, Incheon, South Korea; and Tom John, Austin Hospital, Heidelberg, Australia.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Waddell
authors.affiliation: Erin L. Stewart, Celine Mascaux, Nhu-An Pham, Shingo Sakashita, Jenna Sykes, Lucia Kim, Naoki Yanagawa, Ghassan Allo, Kota Ishizawa, Dennis Wang, Chang-Qi Zhu, Ming Li, Christine Ng, Ni Liu, Melania Pintilie, Petra Martin, Tom John, Igor Jurisica, Natasha B. Leighl, Benjamin G. Neel, Thomas K. Waddell, Frances A. Shepherd, Geoffrey Liu, Ming-Sound Tsao, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; Lucia Kim, Inha University College of Medicine, Incheon, South Korea; and Tom John, Austin Hospital, Heidelberg, Australia.
authors.forename: Frances A
authors.initials: FA
authors.lastname: Shepherd
authors.affiliation: Erin L. Stewart, Celine Mascaux, Nhu-An Pham, Shingo Sakashita, Jenna Sykes, Lucia Kim, Naoki Yanagawa, Ghassan Allo, Kota Ishizawa, Dennis Wang, Chang-Qi Zhu, Ming Li, Christine Ng, Ni Liu, Melania Pintilie, Petra Martin, Tom John, Igor Jurisica, Natasha B. Leighl, Benjamin G. Neel, Thomas K. Waddell, Frances A. Shepherd, Geoffrey Liu, Ming-Sound Tsao, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; Lucia Kim, Inha University College of Medicine, Incheon, South Korea; and Tom John, Austin Hospital, Heidelberg, Australia.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Liu
authors.affiliation: Erin L. Stewart, Celine Mascaux, Nhu-An Pham, Shingo Sakashita, Jenna Sykes, Lucia Kim, Naoki Yanagawa, Ghassan Allo, Kota Ishizawa, Dennis Wang, Chang-Qi Zhu, Ming Li, Christine Ng, Ni Liu, Melania Pintilie, Petra Martin, Tom John, Igor Jurisica, Natasha B. Leighl, Benjamin G. Neel, Thomas K. Waddell, Frances A. Shepherd, Geoffrey Liu, Ming-Sound Tsao, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; Lucia Kim, Inha University College of Medicine, Incheon, South Korea; and Tom John, Austin Hospital, Heidelberg, Australia. Ming.Tsao@uhn.ca.
authors.forename: Ming-Sound
authors.initials: MS
authors.lastname: Tsao
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D000077192:Adenocarcinoma of Lung; D000077716:Afatinib; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism*; D000068818:Cetuximab; D000077547:Crizotinib; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000187:drug effects / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009154:Mutation; D011237:Predictive Value of Tests; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011720:Pyrazoles / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D052999:Quinazolinones / Q000008:administration & dosage; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D011799:Quinazolines; D052999:Quinazolinones; D000077716:Afatinib; C525726:dacomitinib; D000077547:Crizotinib; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D000068818:Cetuximab