Extreme Outlier Analysis Identifies Occult Mitogen-Activated Protein Kinase Pathway Mutations in Patients With Low-Grade Serous Ovarian Cancer.
OBJECTIVE
No effective systemic therapy exists for patients with metastatic low-grade serous (LGS) ovarian cancers. BRAF and KRAS mutations are common in serous borderline (SB) and LGS ovarian cancers, and MEK inhibition has been shown to induce tumor regression in a minority of patients; however, no correlation has been observed between mutation status and clinical response. With the goal of identifying biomarkers of sensitivity to MEK inhibitor treatment, we performed an outlier analysis of a patient who experienced a complete, durable, and ongoing (> 5 years) response to selumetinib, a non-ATP competitive MEK inhibitor.


METHODS
Next-generation sequencing was used to analyze this patient's tumor as well as an additional 28 SB/LGS tumors. Functional characterization of an identified novel alteration of interest was performed.


RESULTS
Analysis of the extraordinary responder's tumor identified a 15-nucleotide deletion in the negative regulatory helix of the MAP2K1 gene encoding for MEK1. Functional characterization demonstrated that this mutant induced extracellular signal-regulated kinase pathway activation, promoted anchorage-independent growth and tumor formation in mice, and retained sensitivity to selumetinib. Analysis of additional LGS/SB tumors identified mutations predicted to induce extracellular signal-regulated kinase pathway activation in 82% (23 of 28), including two patients with BRAF fusions, one of whom achieved an ongoing complete response to MEK inhibitor-based combination therapy.


CONCLUSIONS
Alterations affecting the mitogen-activated protein kinase pathway are present in the majority of patients with LGS ovarian cancer. Next-generation sequencing analysis revealed deletions and fusions that are not detected by older sequencing approaches. These findings, coupled with the observation that a subset of patients with recurrent LGS ovarian cancer experienced dramatic and durable responses to MEK inhibitor therapy, support additional clinical studies of MEK inhibitors in this disease.
Rachel N. Grisham, Brooke E. Sylvester, Helen Won, Deborah DeLair, Zhan Yao, Ronglai Shen, Fanny Dao, Faina Bogomolniy, Vicky Makker, Evis Sala, Tara E. Soumerai, David M. Hyman, Douglas A. Levine, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Memorial Sloan Kettering Cancer Center; Rachel N. Grisham, Gregory McDermott, Vicky Makker, David M. Hyman, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Weill Cornell Medical College; Ricardo Ramirez, Graduate School of Medical Sciences; Nicholas D. Socci and Agnes Viale, Michael F. Berger, and David B. Solit, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, New York, NY; David M. Gershenson, University of Texas MD Anderson Cancer Center, Houston, TX; and John Farley, St Joseph's Hospital and Medical Center, Phoenix, AZ. grishamr@mskcc.org.
Rachel N
RN
Grisham
Rachel N. Grisham, Brooke E. Sylvester, Helen Won, Deborah DeLair, Zhan Yao, Ronglai Shen, Fanny Dao, Faina Bogomolniy, Vicky Makker, Evis Sala, Tara E. Soumerai, David M. Hyman, Douglas A. Levine, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Memorial Sloan Kettering Cancer Center; Rachel N. Grisham, Gregory McDermott, Vicky Makker, David M. Hyman, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Weill Cornell Medical College; Ricardo Ramirez, Graduate School of Medical Sciences; Nicholas D. Socci and Agnes Viale, Michael F. Berger, and David B. Solit, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, New York, NY; David M. Gershenson, University of Texas MD Anderson Cancer Center, Houston, TX; and John Farley, St Joseph's Hospital and Medical Center, Phoenix, AZ.
Brooke E
BE
Sylvester
Rachel N. Grisham, Brooke E. Sylvester, Helen Won, Deborah DeLair, Zhan Yao, Ronglai Shen, Fanny Dao, Faina Bogomolniy, Vicky Makker, Evis Sala, Tara E. Soumerai, David M. Hyman, Douglas A. Levine, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Memorial Sloan Kettering Cancer Center; Rachel N. Grisham, Gregory McDermott, Vicky Makker, David M. Hyman, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Weill Cornell Medical College; Ricardo Ramirez, Graduate School of Medical Sciences; Nicholas D. Socci and Agnes Viale, Michael F. Berger, and David B. Solit, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, New York, NY; David M. Gershenson, University of Texas MD Anderson Cancer Center, Houston, TX; and John Farley, St Joseph's Hospital and Medical Center, Phoenix, AZ.
Helen
H
Won
Rachel N. Grisham, Brooke E. Sylvester, Helen Won, Deborah DeLair, Zhan Yao, Ronglai Shen, Fanny Dao, Faina Bogomolniy, Vicky Makker, Evis Sala, Tara E. Soumerai, David M. Hyman, Douglas A. Levine, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Memorial Sloan Kettering Cancer Center; Rachel N. Grisham, Gregory McDermott, Vicky Makker, David M. Hyman, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Weill Cornell Medical College; Ricardo Ramirez, Graduate School of Medical Sciences; Nicholas D. Socci and Agnes Viale, Michael F. Berger, and David B. Solit, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, New York, NY; David M. Gershenson, University of Texas MD Anderson Cancer Center, Houston, TX; and John Farley, St Joseph's Hospital and Medical Center, Phoenix, AZ.
Gregory
G
McDermott
Rachel N. Grisham, Brooke E. Sylvester, Helen Won, Deborah DeLair, Zhan Yao, Ronglai Shen, Fanny Dao, Faina Bogomolniy, Vicky Makker, Evis Sala, Tara E. Soumerai, David M. Hyman, Douglas A. Levine, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Memorial Sloan Kettering Cancer Center; Rachel N. Grisham, Gregory McDermott, Vicky Makker, David M. Hyman, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Weill Cornell Medical College; Ricardo Ramirez, Graduate School of Medical Sciences; Nicholas D. Socci and Agnes Viale, Michael F. Berger, and David B. Solit, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, New York, NY; David M. Gershenson, University of Texas MD Anderson Cancer Center, Houston, TX; and John Farley, St Joseph's Hospital and Medical Center, Phoenix, AZ.
Deborah
D
DeLair
Rachel N. Grisham, Brooke E. Sylvester, Helen Won, Deborah DeLair, Zhan Yao, Ronglai Shen, Fanny Dao, Faina Bogomolniy, Vicky Makker, Evis Sala, Tara E. Soumerai, David M. Hyman, Douglas A. Levine, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Memorial Sloan Kettering Cancer Center; Rachel N. Grisham, Gregory McDermott, Vicky Makker, David M. Hyman, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Weill Cornell Medical College; Ricardo Ramirez, Graduate School of Medical Sciences; Nicholas D. Socci and Agnes Viale, Michael F. Berger, and David B. Solit, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, New York, NY; David M. Gershenson, University of Texas MD Anderson Cancer Center, Houston, TX; and John Farley, St Joseph's Hospital and Medical Center, Phoenix, AZ.
Ricardo
R
Ramirez
Rachel N. Grisham, Brooke E. Sylvester, Helen Won, Deborah DeLair, Zhan Yao, Ronglai Shen, Fanny Dao, Faina Bogomolniy, Vicky Makker, Evis Sala, Tara E. Soumerai, David M. Hyman, Douglas A. Levine, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Memorial Sloan Kettering Cancer Center; Rachel N. Grisham, Gregory McDermott, Vicky Makker, David M. Hyman, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Weill Cornell Medical College; Ricardo Ramirez, Graduate School of Medical Sciences; Nicholas D. Socci and Agnes Viale, Michael F. Berger, and David B. Solit, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, New York, NY; David M. Gershenson, University of Texas MD Anderson Cancer Center, Houston, TX; and John Farley, St Joseph's Hospital and Medical Center, Phoenix, AZ.
Zhan
Z
Yao
Rachel N. Grisham, Brooke E. Sylvester, Helen Won, Deborah DeLair, Zhan Yao, Ronglai Shen, Fanny Dao, Faina Bogomolniy, Vicky Makker, Evis Sala, Tara E. Soumerai, David M. Hyman, Douglas A. Levine, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Memorial Sloan Kettering Cancer Center; Rachel N. Grisham, Gregory McDermott, Vicky Makker, David M. Hyman, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Weill Cornell Medical College; Ricardo Ramirez, Graduate School of Medical Sciences; Nicholas D. Socci and Agnes Viale, Michael F. Berger, and David B. Solit, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, New York, NY; David M. Gershenson, University of Texas MD Anderson Cancer Center, Houston, TX; and John Farley, St Joseph's Hospital and Medical Center, Phoenix, AZ.
Ronglai
R
Shen
Rachel N. Grisham, Brooke E. Sylvester, Helen Won, Deborah DeLair, Zhan Yao, Ronglai Shen, Fanny Dao, Faina Bogomolniy, Vicky Makker, Evis Sala, Tara E. Soumerai, David M. Hyman, Douglas A. Levine, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Memorial Sloan Kettering Cancer Center; Rachel N. Grisham, Gregory McDermott, Vicky Makker, David M. Hyman, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Weill Cornell Medical College; Ricardo Ramirez, Graduate School of Medical Sciences; Nicholas D. Socci and Agnes Viale, Michael F. Berger, and David B. Solit, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, New York, NY; David M. Gershenson, University of Texas MD Anderson Cancer Center, Houston, TX; and John Farley, St Joseph's Hospital and Medical Center, Phoenix, AZ.
Fanny
F
Dao
Rachel N. Grisham, Brooke E. Sylvester, Helen Won, Deborah DeLair, Zhan Yao, Ronglai Shen, Fanny Dao, Faina Bogomolniy, Vicky Makker, Evis Sala, Tara E. Soumerai, David M. Hyman, Douglas A. Levine, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Memorial Sloan Kettering Cancer Center; Rachel N. Grisham, Gregory McDermott, Vicky Makker, David M. Hyman, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Weill Cornell Medical College; Ricardo Ramirez, Graduate School of Medical Sciences; Nicholas D. Socci and Agnes Viale, Michael F. Berger, and David B. Solit, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, New York, NY; David M. Gershenson, University of Texas MD Anderson Cancer Center, Houston, TX; and John Farley, St Joseph's Hospital and Medical Center, Phoenix, AZ.
Faina
F
Bogomolniy
Rachel N. Grisham, Brooke E. Sylvester, Helen Won, Deborah DeLair, Zhan Yao, Ronglai Shen, Fanny Dao, Faina Bogomolniy, Vicky Makker, Evis Sala, Tara E. Soumerai, David M. Hyman, Douglas A. Levine, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Memorial Sloan Kettering Cancer Center; Rachel N. Grisham, Gregory McDermott, Vicky Makker, David M. Hyman, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Weill Cornell Medical College; Ricardo Ramirez, Graduate School of Medical Sciences; Nicholas D. Socci and Agnes Viale, Michael F. Berger, and David B. Solit, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, New York, NY; David M. Gershenson, University of Texas MD Anderson Cancer Center, Houston, TX; and John Farley, St Joseph's Hospital and Medical Center, Phoenix, AZ.
Vicky
V
Makker
Rachel N. Grisham, Brooke E. Sylvester, Helen Won, Deborah DeLair, Zhan Yao, Ronglai Shen, Fanny Dao, Faina Bogomolniy, Vicky Makker, Evis Sala, Tara E. Soumerai, David M. Hyman, Douglas A. Levine, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Memorial Sloan Kettering Cancer Center; Rachel N. Grisham, Gregory McDermott, Vicky Makker, David M. Hyman, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Weill Cornell Medical College; Ricardo Ramirez, Graduate School of Medical Sciences; Nicholas D. Socci and Agnes Viale, Michael F. Berger, and David B. Solit, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, New York, NY; David M. Gershenson, University of Texas MD Anderson Cancer Center, Houston, TX; and John Farley, St Joseph's Hospital and Medical Center, Phoenix, AZ.
Evis
E
Sala
Rachel N. Grisham, Brooke E. Sylvester, Helen Won, Deborah DeLair, Zhan Yao, Ronglai Shen, Fanny Dao, Faina Bogomolniy, Vicky Makker, Evis Sala, Tara E. Soumerai, David M. Hyman, Douglas A. Levine, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Memorial Sloan Kettering Cancer Center; Rachel N. Grisham, Gregory McDermott, Vicky Makker, David M. Hyman, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Weill Cornell Medical College; Ricardo Ramirez, Graduate School of Medical Sciences; Nicholas D. Socci and Agnes Viale, Michael F. Berger, and David B. Solit, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, New York, NY; David M. Gershenson, University of Texas MD Anderson Cancer Center, Houston, TX; and John Farley, St Joseph's Hospital and Medical Center, Phoenix, AZ.
Tara E
TE
Soumerai
Rachel N. Grisham, Brooke E. Sylvester, Helen Won, Deborah DeLair, Zhan Yao, Ronglai Shen, Fanny Dao, Faina Bogomolniy, Vicky Makker, Evis Sala, Tara E. Soumerai, David M. Hyman, Douglas A. Levine, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Memorial Sloan Kettering Cancer Center; Rachel N. Grisham, Gregory McDermott, Vicky Makker, David M. Hyman, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Weill Cornell Medical College; Ricardo Ramirez, Graduate School of Medical Sciences; Nicholas D. Socci and Agnes Viale, Michael F. Berger, and David B. Solit, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, New York, NY; David M. Gershenson, University of Texas MD Anderson Cancer Center, Houston, TX; and John Farley, St Joseph's Hospital and Medical Center, Phoenix, AZ.
David M
DM
Hyman
Rachel N. Grisham, Brooke E. Sylvester, Helen Won, Deborah DeLair, Zhan Yao, Ronglai Shen, Fanny Dao, Faina Bogomolniy, Vicky Makker, Evis Sala, Tara E. Soumerai, David M. Hyman, Douglas A. Levine, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Memorial Sloan Kettering Cancer Center; Rachel N. Grisham, Gregory McDermott, Vicky Makker, David M. Hyman, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Weill Cornell Medical College; Ricardo Ramirez, Graduate School of Medical Sciences; Nicholas D. Socci and Agnes Viale, Michael F. Berger, and David B. Solit, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, New York, NY; David M. Gershenson, University of Texas MD Anderson Cancer Center, Houston, TX; and John Farley, St Joseph's Hospital and Medical Center, Phoenix, AZ.
Nicholas D
ND
Socci
Rachel N. Grisham, Brooke E. Sylvester, Helen Won, Deborah DeLair, Zhan Yao, Ronglai Shen, Fanny Dao, Faina Bogomolniy, Vicky Makker, Evis Sala, Tara E. Soumerai, David M. Hyman, Douglas A. Levine, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Memorial Sloan Kettering Cancer Center; Rachel N. Grisham, Gregory McDermott, Vicky Makker, David M. Hyman, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Weill Cornell Medical College; Ricardo Ramirez, Graduate School of Medical Sciences; Nicholas D. Socci and Agnes Viale, Michael F. Berger, and David B. Solit, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, New York, NY; David M. Gershenson, University of Texas MD Anderson Cancer Center, Houston, TX; and John Farley, St Joseph's Hospital and Medical Center, Phoenix, AZ.
Agnes
A
Viale
Rachel N. Grisham, Brooke E. Sylvester, Helen Won, Deborah DeLair, Zhan Yao, Ronglai Shen, Fanny Dao, Faina Bogomolniy, Vicky Makker, Evis Sala, Tara E. Soumerai, David M. Hyman, Douglas A. Levine, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Memorial Sloan Kettering Cancer Center; Rachel N. Grisham, Gregory McDermott, Vicky Makker, David M. Hyman, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Weill Cornell Medical College; Ricardo Ramirez, Graduate School of Medical Sciences; Nicholas D. Socci and Agnes Viale, Michael F. Berger, and David B. Solit, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, New York, NY; David M. Gershenson, University of Texas MD Anderson Cancer Center, Houston, TX; and John Farley, St Joseph's Hospital and Medical Center, Phoenix, AZ.
David M
DM
Gershenson
Rachel N. Grisham, Brooke E. Sylvester, Helen Won, Deborah DeLair, Zhan Yao, Ronglai Shen, Fanny Dao, Faina Bogomolniy, Vicky Makker, Evis Sala, Tara E. Soumerai, David M. Hyman, Douglas A. Levine, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Memorial Sloan Kettering Cancer Center; Rachel N. Grisham, Gregory McDermott, Vicky Makker, David M. Hyman, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Weill Cornell Medical College; Ricardo Ramirez, Graduate School of Medical Sciences; Nicholas D. Socci and Agnes Viale, Michael F. Berger, and David B. Solit, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, New York, NY; David M. Gershenson, University of Texas MD Anderson Cancer Center, Houston, TX; and John Farley, St Joseph's Hospital and Medical Center, Phoenix, AZ.
John
J
Farley
Rachel N. Grisham, Brooke E. Sylvester, Helen Won, Deborah DeLair, Zhan Yao, Ronglai Shen, Fanny Dao, Faina Bogomolniy, Vicky Makker, Evis Sala, Tara E. Soumerai, David M. Hyman, Douglas A. Levine, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Memorial Sloan Kettering Cancer Center; Rachel N. Grisham, Gregory McDermott, Vicky Makker, David M. Hyman, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Weill Cornell Medical College; Ricardo Ramirez, Graduate School of Medical Sciences; Nicholas D. Socci and Agnes Viale, Michael F. Berger, and David B. Solit, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, New York, NY; David M. Gershenson, University of Texas MD Anderson Cancer Center, Houston, TX; and John Farley, St Joseph's Hospital and Medical Center, Phoenix, AZ.
Douglas A
DA
Levine
Rachel N. Grisham, Brooke E. Sylvester, Helen Won, Deborah DeLair, Zhan Yao, Ronglai Shen, Fanny Dao, Faina Bogomolniy, Vicky Makker, Evis Sala, Tara E. Soumerai, David M. Hyman, Douglas A. Levine, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Memorial Sloan Kettering Cancer Center; Rachel N. Grisham, Gregory McDermott, Vicky Makker, David M. Hyman, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Weill Cornell Medical College; Ricardo Ramirez, Graduate School of Medical Sciences; Nicholas D. Socci and Agnes Viale, Michael F. Berger, and David B. Solit, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, New York, NY; David M. Gershenson, University of Texas MD Anderson Cancer Center, Houston, TX; and John Farley, St Joseph's Hospital and Medical Center, Phoenix, AZ.
Neal
N
Rosen
Rachel N. Grisham, Brooke E. Sylvester, Helen Won, Deborah DeLair, Zhan Yao, Ronglai Shen, Fanny Dao, Faina Bogomolniy, Vicky Makker, Evis Sala, Tara E. Soumerai, David M. Hyman, Douglas A. Levine, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Memorial Sloan Kettering Cancer Center; Rachel N. Grisham, Gregory McDermott, Vicky Makker, David M. Hyman, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Weill Cornell Medical College; Ricardo Ramirez, Graduate School of Medical Sciences; Nicholas D. Socci and Agnes Viale, Michael F. Berger, and David B. Solit, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, New York, NY; David M. Gershenson, University of Texas MD Anderson Cancer Center, Houston, TX; and John Farley, St Joseph's Hospital and Medical Center, Phoenix, AZ.
Michael F
MF
Berger
Rachel N. Grisham, Brooke E. Sylvester, Helen Won, Deborah DeLair, Zhan Yao, Ronglai Shen, Fanny Dao, Faina Bogomolniy, Vicky Makker, Evis Sala, Tara E. Soumerai, David M. Hyman, Douglas A. Levine, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Memorial Sloan Kettering Cancer Center; Rachel N. Grisham, Gregory McDermott, Vicky Makker, David M. Hyman, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Weill Cornell Medical College; Ricardo Ramirez, Graduate School of Medical Sciences; Nicholas D. Socci and Agnes Viale, Michael F. Berger, and David B. Solit, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, New York, NY; David M. Gershenson, University of Texas MD Anderson Cancer Center, Houston, TX; and John Farley, St Joseph's Hospital and Medical Center, Phoenix, AZ.
David R
DR
Spriggs
Rachel N. Grisham, Brooke E. Sylvester, Helen Won, Deborah DeLair, Zhan Yao, Ronglai Shen, Fanny Dao, Faina Bogomolniy, Vicky Makker, Evis Sala, Tara E. Soumerai, David M. Hyman, Douglas A. Levine, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Memorial Sloan Kettering Cancer Center; Rachel N. Grisham, Gregory McDermott, Vicky Makker, David M. Hyman, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Weill Cornell Medical College; Ricardo Ramirez, Graduate School of Medical Sciences; Nicholas D. Socci and Agnes Viale, Michael F. Berger, and David B. Solit, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, New York, NY; David M. Gershenson, University of Texas MD Anderson Cancer Center, Houston, TX; and John Farley, St Joseph's Hospital and Medical Center, Phoenix, AZ.
Carol A
CA
Aghajanian
Rachel N. Grisham, Brooke E. Sylvester, Helen Won, Deborah DeLair, Zhan Yao, Ronglai Shen, Fanny Dao, Faina Bogomolniy, Vicky Makker, Evis Sala, Tara E. Soumerai, David M. Hyman, Douglas A. Levine, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Memorial Sloan Kettering Cancer Center; Rachel N. Grisham, Gregory McDermott, Vicky Makker, David M. Hyman, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Weill Cornell Medical College; Ricardo Ramirez, Graduate School of Medical Sciences; Nicholas D. Socci and Agnes Viale, Michael F. Berger, and David B. Solit, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, New York, NY; David M. Gershenson, University of Texas MD Anderson Cancer Center, Houston, TX; and John Farley, St Joseph's Hospital and Medical Center, Phoenix, AZ.
David B
DB
Solit
Rachel N. Grisham, Brooke E. Sylvester, Helen Won, Deborah DeLair, Zhan Yao, Ronglai Shen, Fanny Dao, Faina Bogomolniy, Vicky Makker, Evis Sala, Tara E. Soumerai, David M. Hyman, Douglas A. Levine, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Memorial Sloan Kettering Cancer Center; Rachel N. Grisham, Gregory McDermott, Vicky Makker, David M. Hyman, Neal Rosen, Michael F. Berger, David R. Spriggs, Carol A. Aghajanian, David B. Solit, and Gopa Iyer, Weill Cornell Medical College; Ricardo Ramirez, Graduate School of Medical Sciences; Nicholas D. Socci and Agnes Viale, Michael F. Berger, and David B. Solit, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, New York, NY; David M. Gershenson, University of Texas MD Anderson Cancer Center, Houston, TX; and John Farley, St Joseph's Hospital and Medical Center, Phoenix, AZ.
Gopa
G
Iyer
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics*; D000077216:Carcinoma, Ovarian Epithelial; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics*; D051379:Mice; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D041681:NIH 3T3 Cells; D060787:Neoplasm Grading; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D014410:Tumor Stem Cell Assay
C517975:AZD 6244; D001562:Benzimidazoles; D014408:Biomarkers, Tumor; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human