title: Combined BRAF and MEK Inhibition With Dabrafenib and Trametinib in BRAF V600-Mutant Colorectal Cancer.
abstract: OBJECTIVE
  To evaluate dabrafenib, a selective BRAF inhibitor, combined with trametinib, a selective MEK inhibitor, in patients with BRAF V600-mutant metastatic colorectal cancer (mCRC).
  
  
  METHODS
  A total of 43 patients with BRAF V600-mutant mCRC were treated with dabrafenib (150 mg twice daily) plus trametinib (2 mg daily), 17 of whom were enrolled onto a pharmacodynamic cohort undergoing mandatory biopsies before and during treatment. Archival tissues were analyzed for microsatellite instability, PTEN status, and 487-gene sequencing. Patient-derived xenografts were established from core biopsy samples.
  
  
  RESULTS
  Of 43 patients, five (12%) achieved a partial response or better, including one (2%) complete response, with duration of response > 36 months; 24 patients (56%) achieved stable disease as best confirmed response. Ten patients (23%) remained in the study > 6 months. All nine evaluable during-treatment biopsies had reduced levels of phosphorylated ERK relative to pretreatment biopsies (average decrease ± standard deviation, 47% ± 24%). Mutational analysis revealed that the patient achieving a complete response and two of three evaluable patients achieving a partial response had PIK3CA mutations. Neither PTEN loss nor microsatellite instability correlated with efficacy. Responses to dabrafenib plus trametinib were comparable in patient-derived xenograft-bearing mice and the biopsied lesions from each corresponding patient.
  
  
  CONCLUSIONS
  The combination of dabrafenib plus trametinib has activity in a subset of patients with BRAF V600-mutant mCRC. Mitogen-activated protein kinase signaling was inhibited in all patients evaluated, but to a lesser degree than observed in BRAF-mutant melanoma with dabrafenib alone. PIK3CA mutations were identified in responding patients and thus do not preclude response to this regimen. Additional studies targeting the mitogen-activated protein kinase pathway in this disease are warranted.
authors.affiliation: Ryan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE. rbcorcoran@partners.org.
authors.forename: Ryan B
authors.initials: RB
authors.lastname: Corcoran
authors.affiliation: Ryan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
authors.forename: Chloe E
authors.initials: CE
authors.lastname: Atreya
authors.affiliation: Ryan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
authors.forename: Gerald S
authors.initials: GS
authors.lastname: Falchook
authors.affiliation: Ryan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
authors.forename: Eunice L
authors.initials: EL
authors.lastname: Kwak
authors.affiliation: Ryan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
authors.forename: David P
authors.initials: DP
authors.lastname: Ryan
authors.affiliation: Ryan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Bendell
authors.affiliation: Ryan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
authors.forename: Omid
authors.initials: O
authors.lastname: Hamid
authors.affiliation: Ryan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
authors.forename: Wells A
authors.initials: WA
authors.lastname: Messersmith
authors.affiliation: Ryan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
authors.forename: Adil
authors.initials: A
authors.lastname: Daud
authors.affiliation: Ryan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
authors.affiliation: Ryan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
authors.forename: Mariaelena
authors.initials: M
authors.lastname: Pierobon
authors.affiliation: Ryan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.affiliation: Ryan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Cunningham
authors.affiliation: Ryan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
authors.forename: Shonda
authors.initials: S
authors.lastname: Little
authors.affiliation: Ryan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
authors.forename: Keith
authors.initials: K
authors.lastname: Orford
authors.affiliation: Ryan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
authors.forename: Monica
authors.initials: M
authors.lastname: Motwani
authors.affiliation: Ryan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Ryan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
authors.forename: Kiran
authors.initials: K
authors.lastname: Patel
authors.affiliation: Ryan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
authors.forename: Alan P
authors.initials: AP
authors.lastname: Venook
authors.affiliation: Ryan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
authors.forename: Scott
authors.initials: S
authors.lastname: Kopetz
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001706:Biopsy; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D010091:Oximes / Q000008:administration & dosage; D051059:PTEN Phosphohydrolase / Q000235:genetics; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics*; D011728:Pyridones / Q000008:administration & dosage; D011744:Pyrimidinones / Q000008:administration & dosage; D023041:Xenograft Model Antitumor Assays
chemical_list: D007093:Imidazoles; D010091:Oximes; D011728:Pyridones; D011744:Pyrimidinones; C560077:trametinib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C561627:dabrafenib