Efficacy of intermittent combined RAF and MEK inhibition in a patient with concurrent BRAF- and NRAS-mutant malignancies

Cancer Discovery

Volumn 4, Issue 5, 2014, Pages 538-545

  Abdel Wahab, Omar ^a,i   Klimek, Virginia M ^a,i   Gaskell, Alisa A ^f   Viale, Agnes ^f   Cheng, Donavan ^d,f   Kim, Eunhee ^e   Rampal, Raajit ^a,i   Bluth, Mark ^e   Harding, James J ^b,i   Callahan, Margaret K ^c,i   Merghoub, Taha ^g   Berger, Michael F ^d,f   Solit, David B ^f,i   Rosen, Neal ^h,i   Levine, Ross L ^a,i   Chapman, Paul B ^c,i  

^a Leukemia Service   (United States)

^b Gastrointestinal Oncology Service   (United States)

^c Melanoma and Immunotherapeutics Service Department of Medicine   (United States)

^d Molecular Diagnostics Service Department of Pathology   (United States)

^e Department of Radiology ^*

^f Center for Molecular Oncology   (United States)

^g Ludwig Center for Cancer Immunotherapy   (United States)

^h MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

ⁱ WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

B RAF KINASE; COBIMETINIB; DNA; VEMURAFENIB; ANTINEOPLASTIC AGENT; AZETIDINE DERIVATIVE; BRAF PROTEIN, HUMAN; GDC-0973; GUANOSINE TRIPHOSPHATASE; INDOLE DERIVATIVE; MEMBRANE PROTEIN; NRAS PROTEIN, HUMAN; PIPERIDINE DERIVATIVE; SULFONAMIDE;

AGED; ARTICLE; BONE MARROW EXAMINATION; CANCER STAGING; CASE REPORT; CHRONIC MYELOMONOCYTIC LEUKEMIA; COMPUTER ASSISTED TOMOGRAPHY; DRUG EFFICACY; DRUG INTERMITTENT THERAPY; FLOW CYTOMETRY; GENE MUTATION; GENETIC ANALYSIS; HUMAN; HUMAN CELL; LEUKOCYTE COUNT; MALE; MELANOMA; ONCOGENE N RAS; POLYMERASE CHAIN REACTION; SPLEEN; ANTAGONISTS AND INHIBITORS; CELL PROLIFERATION; CHEMICALLY INDUCED; DRUG ADMINISTRATION; DRUG EFFECTS; GENETICS; LEUKEMIA; MUTATION; PATHOLOGY; SIGNAL TRANSDUCTION; TUMOR CELL LINE; TUMOR EMBOLISM;

AGED; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; AZETIDINES; CELL LINE, TUMOR; CELL PROLIFERATION; DNA, NEOPLASM; DRUG ADMINISTRATION SCHEDULE; GTP PHOSPHOHYDROLASES; HUMANS; INDOLES; LEUKEMIA; MALE; MAP KINASE SIGNALING SYSTEM; MELANOMA; MEMBRANE PROTEINS; MUTATION; NEOPLASTIC CELLS, CIRCULATING; PIPERIDINES; PROTO-ONCOGENE PROTEINS B-RAF; SULFONAMIDES;

EID: 84899512149     PISSN: 21598274     EISSN: 21598290     Source Type: Journal    
DOI: 10.1158/2159-8290.CD-13-1038     Document Type: Article

References (21)

1. Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011; 364: 2507-16.
2. Joseph E, Pratilas C, Poulikakos P, Tadi M, Wang W, Taylor B, et al. The RAF inhibitor PLX4032 inhibits ERK signaling and tumor cell proliferation in a V600E BRAF-selective manner. Proc Natl Acad Sci U S A 2010; 107: 14903-8.
3. Poulikakos P, Zhang C, Bollag G, Shokat K, Rosen N. RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF. Nature 2010; 464: 427-30.
4. Heidorn SJ, Milagre C, Whittaker S, Nourry A, Niculescu-Duvas I, Dhomen N, et al. Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF. Cell 2010; 140: 209-21.
5. Callahan MK, Rampal R, Harding JJ, Klimek VM, Chung YR, Merghoub T, et al. Progression of RAS-mutant leukemia during RAF inhibitor treatment. N Engl J Med 2012; 367: 2316-21.
6. Choo EF, Belvin M, Boggs J, Deng Y, Hoeflich KP, Ly J, et al. Preclinical disposition of GDC-0973 and prospective and retrospective analysis of human dose and efficacy predictions. Drug Metab Dispos 2012; 40: 919-27.
7. Huggett JF, Foy CA, Benes V, Emslie K, Garson JA, Haynes R, et al. Guidelines for minimum information for publication of quantitative digital PCR experiments. Clin Chem 2013; 59: 892-902.
8. Hindson BJ, Ness KD, Masquelier DA, Belgrader P, Heredia NJ, Makarewicz AJ, et al. High-throughput droplet digital PCR system for absolute quantitation of DNA copy number. Anal Chem 2011; 83: 8604-10.
9. Wagle N, Berger M, Davis M, Blumenstiel B, Defelice M, Pochanard P, et al. High-throughput detection of actionable genomic alterations in clinical tumor samples by targeted, massively parallel sequencing. Cancer Discov 2012; 2: 82-93.
10. Fine B, Hodakoski C, Koujak S, Su T, Saal LH, Maurer M, et al. Activation of the PI3K pathway in cancer through inhibition of PTEN by exchange factor P-REX2a. Science 2009; 325: 1261-5.
11. Itzykson R, Kosmider O, Renneville A, Gelsi-Boyer V, Meggendorfer M, Morabito M, et al. Prognostic score including gene mutations in chronic myelomonocytic leukemia. J Clin Oncol 2013; 31: 2428-36.
12. Flaherty KT, Infante JR, Daud A, Gonzalez R, Kefford RF, Sosman J, et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med 2012; 367: 1694-703.
13. Das Thakur M, Salangsang F, Landman AS, Sellers WR, Pryer NK, Levesque MP, et al. Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance. Nature 2013; 494: 251-5.
14. Borthakur G, Popplewell L, Boyiadzis M, Foran JM, Platzbecker U, Vey N, et al. Phase I/II trial of the MEK1/2 inhibitor trametinib (GSK1120212) in relapsed/refractory myeloid malignancies: evidence of activity in patients with RAS mutation-positive disease [abstract]. In: Proceedings of the 54th ASH Annual Meeting and Exposition; 2012 Dec 8-11; Atlanta, GA. Abstract nr 677.
15. Jain N, Curran E, Iyengar NM, Diaz-Flores E, Kunnavakkam R, Popplewell L, et al. Phase II study of the oral MEK inhibitor selumetinib (AZD6244) in advanced acute myeloid leukemia (AML). J Clin Oncol 30, 2012 (suppl; abstr 6582).
16. Patel JP, Gonen M, Figueroa ME, Fernandez H, Sun Z, Racevskis J, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med 2012; 366: 1079-89.
17. Whale AS, Huggett JF, Cowen S, Speirs V, Shaw J, Ellison S, et al. Comparison of microfluidic digital PCR and conventional quantitative PCR for measuring copy number variation. Nucleic Acids Res 2012; 40: e82.
18. Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 2009; 25: 1754-60.
19. DePristo M, Banks E, Poplin R, Garimella K, Maguire J, Hartl C, et al. A framework for variation discovery and genotyping using nextgeneration DNA sequencing data. Nat Genet 2011; 43: 491-8.
20. Cibulskis K, Lawrence M, Carter S, Sivachenko A, Jaffe D, Sougnez C, et al. Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nat Biotechnol 2013; 31: 213-9.
21. Thorvaldsdóttir H, Robinson J, Mesirov J. Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration. Brief Bioinform 2013; 14: 178-92.