Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2013

Open Access 01-12-2013 | Review

B-Raf and the inhibitors: from bench to bedside

Authors: Tiangui Huang, Michael Karsy, Jian Zhuge, Minghao Zhong, Delong Liu

Published in: Journal of Hematology & Oncology | Issue 1/2013

Login to get access

Abstract

The B-Raf protein is a key signaling molecule in the mitogen activated protein kinase (MAPK) signaling pathway and has been implicated in the pathogenesis of a variety of cancers. An important V600E mutation has been identified and can cause constitutive B-Raf activation. Recent studies have evaluated a variety of small molecule inhibitors targeting B-Raf, including PLX4032/vemurafenib, dabrafenib, LGX818, GDC0879, XL281, ARQ736, PLX3603 (RO5212054), and RAF265. Therapeutic resistance has been identified and various mechanisms described. This review also discussed the current understanding of B-Raf signaling mechanism, methods of mutation detection, treatment strategies as well as potential methods of overcoming therapeutic resistance.
Appendix
Available only for authorised users
Literature
1.
Mark GE, Rapp UR: Primary structure of v-raf: relatedness to the src family of oncogenes. Science. 1984, 224 (4646): 285-289. 10.1126/science.6324342.CrossRefPubMed
2.
Roskoski R: RAF protein-serine/threonine kinases: structure and regulation. Biochem Biophys Res Commun. 2010, 399 (3): 313-317. 10.1016/j.bbrc.2010.07.092.CrossRefPubMed
3.
Zebisch A, Troppmair J: Back to the roots: the remarkable RAF oncogene story. Cell Mol Life Sci. 2006, 63 (11): 1314-1330. 10.1007/s00018-006-6005-y.CrossRefPubMed
4.
Eychene A, Barnier JV, Apiou F, Dutrillaux B, Calothy G: Chromosomal assignment of two human B-raf(Rmil) proto-oncogene loci: B-raf-1 encoding the p94Braf/Rmil and B-raf-2, a processed pseudogene. Oncogene. 1992, 7 (8): 1657-1660.PubMed
5.
Pratilas CA, Solit DB: Targeting the mitogen-activated protein kinase pathway: physiological feedback and drug response. Clin Cancer Res. 2010, 16 (13): 3329-3334. 10.1158/1078-0432.CCR-09-3064.PubMedCentralCrossRefPubMed
6.
Ikawa S, Fukui M, Ueyama Y, Tamaoki N, Yamamoto T, Toyoshima K: B-raf, a new member of the raf family, is activated by DNA rearrangement. Mol Cell Biol. 1988, 8 (6): 2651-2654.PubMedCentralCrossRefPubMed
7.
8.
Furqan M, Mukhi N, Lee B, Liu D: Dysregulation of JAK-STAT pathway in hematological malignancies and JAK inhibitors for clinical application. Biomarker Research. 2013, 1 (1): 5-PubMedCentralCrossRefPubMed
9.
Zhao W, Du Y, Ho W, Fu X, Zhao Z: JAK2V617F and p53 mutations coexist in erythroleukemia and megakaryoblastic leukemic cell lines. Exp Hematol Oncol. 2012, 1 (1): 15-10.1186/2162-3619-1-15.PubMedCentralCrossRefPubMed
10.
Huang T, Zhuge J, Zhang W: Sensitive detection of BRAF V600E mutation by Amplification Refractory Mutation System (ARMS)-PCR. Biomarker Research. 2013, 1 (1): 3-PubMedCentralCrossRefPubMed
11.
12.
Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W: Mutations of the BRAF gene in human cancer. Nature. 2002, 417 (6892): 949-954. 10.1038/nature00766.CrossRefPubMed
13.
Domingo E, Laiho P, Ollikainen M, Pinto M, Wang L, French AJ, Westra J, Frebourg T, Espin E, Armengol M: BRAF screening as a low-cost effective strategy for simplifying HNPCC genetic testing. J Med Genet. 2004, 41 (9): 664-668. 10.1136/jmg.2004.020651.PubMedCentralCrossRefPubMed
14.
Kebebew E, Weng J, Bauer J, Ranvier G, Clark OH, Duh QY, Shibru D, Bastian B, Griffin A: The prevalence and prognostic value of BRAF mutation in thyroid cancer. Ann Surg. 2007, 246 (3): 466-470. 10.1097/SLA.0b013e318148563d. discussion 470-461PubMedCentralCrossRefPubMed
15.
Ziai J, Hui P: BRAF mutation testing in clinical practice. Expert Rev Mol Diagn. 2012, 12 (2): 127-138. 10.1586/erm.12.1.CrossRefPubMed
16.
Poulikakos PI, Rosen N: Mutant BRAF melanomas–dependence and resistance. Cancer Cell. 2011, 19 (1): 11-15. 10.1016/j.ccr.2011.01.008.CrossRefPubMed
17.
Kumar R, Angelini S, Czene K, Sauroja I, Hahka-Kemppinen M, Pyrhonen S, Hemminki K: BRAF mutations in metastatic melanoma: a possible association with clinical outcome. Clin Cancer Res. 2003, 9 (9): 3362-3368.PubMed
18.
Su F, Bradley WD, Wang Q, Yang H, Xu L, Higgins B, Kolinsky K, Packman K, Kim MJ, Trunzer K: Resistance to selective BRAF inhibition can be mediated by modest upstream pathway activation. Cancer Res. 2012, 72 (4): 969-978. 10.1158/0008-5472.CAN-11-1875.CrossRefPubMed
19.
Luke JJ, Hodi FS: Vemurafenib and BRAF inhibition: a new class of treatment for metastatic melanoma. Clin Cancer Res. 2012, 18 (1): 9-14. 10.1158/1078-0432.CCR-11-2197.CrossRefPubMed
20.
Pollock PM, Harper UL, Hansen KS, Yudt LM, Stark M, Robbins CM, Moses TY, Hostetter G, Wagner U, Kakareka J: High frequency of BRAF mutations in nevi. Nat Genet. 2003, 33 (1): 19-20. 10.1038/ng1054.CrossRefPubMed
21.
Dong J, Phelps RG, Qiao R, Yao S, Benard O, Ronai Z, Aaronson SA: BRAF oncogenic mutations correlate with progression rather than initiation of human melanoma. Cancer Res. 2003, 63 (14): 3883-3885.PubMed
22.
Dankort D, Curley DP, Cartlidge RA, Nelson B, Karnezis AN, Damsky WE, You MJ, DePinho RA, McMahon M, Bosenberg M: Braf(V600E) cooperates with Pten loss to induce metastatic melanoma. Nat Genet. 2009, 41 (5): 544-552. 10.1038/ng.356.PubMedCentralCrossRefPubMed
23.
Cohen Y, Xing M, Mambo E, Guo Z, Wu G, Trink B, Beller U, Westra WH, Ladenson PW, Sidransky D: BRAF mutation in papillary thyroid carcinoma. J Natl Cancer Inst. 2003, 95 (8): 625-627. 10.1093/jnci/95.8.625.CrossRefPubMed
24.
Trovisco V, Vieira De Castro I, Soares P, Maximo V, Silva P, Magalhaes J, Abrosimov A, Guiu XM, Sobrinho-Simoes M: BRAF mutations are associated with some histological types of papillary thyroid carcinoma. J Pathol. 2004, 202 (2): 247-251. 10.1002/path.1511.CrossRefPubMed
25.
Nikiforova MN, Kimura ET, Gandhi M, Biddinger PW, Knauf JA, Basolo F, Zhu Z, Giannini R, Salvatore G, Fusco A: BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J Clin Endocrinol Metab. 2003, 88 (11): 5399-5404. 10.1210/jc.2003-030838.CrossRefPubMed
26.
Xing M, Westra WH, Tufano RP, Cohen Y, Rosenbaum E, Rhoden KJ, Carson KA, Vasko V, Larin A, Tallini G: BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer. J Clin Endocrinol Metab. 2005, 90 (12): 6373-6379. 10.1210/jc.2005-0987.CrossRefPubMed
27.
Xing M: BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications. Endocr Rev. 2007, 28 (7): 742-762. 10.1210/er.2007-0007.CrossRefPubMed
28.
29.
Vasko V, Hu S, Wu G, Xing JC, Larin A, Savchenko V, Trink B, Xing M: High prevalence and possible de novo formation of BRAF mutation in metastasized papillary thyroid cancer in lymph nodes. J Clin Endocrinol Metab. 2005, 90 (9): 5265-5269. 10.1210/jc.2004-2353.CrossRefPubMed
30.
Knauf JA, Ma X, Smith EP, Zhang L, Mitsutake N, Liao XH, Refetoff S, Nikiforov YE, Fagin JA: Targeted expression of BRAFV600E in thyroid cells of transgenic mice results in papillary thyroid cancers that undergo dedifferentiation. Cancer Res. 2005, 65 (10): 4238-4245. 10.1158/0008-5472.CAN-05-0047.CrossRefPubMed
31.
Charles RP, Iezza G, Amendola E, Dankort D, McMahon M: Mutationally activated BRAF(V600E) elicits papillary thyroid cancer in the adult mouse. Cancer Res. 2011, 71 (11): 3863-3871. 10.1158/0008-5472.CAN-10-4463.PubMedCentralCrossRefPubMed
32.
Guerra A, Sapio MR, Marotta V, Campanile E, Rossi S, Forno I, Fugazzola L, Budillon A, Moccia T, Fenzi G: The primary occurrence of BRAF(V600E) is a rare clonal event in papillary thyroid carcinoma. J Clin Endocrinol Metab. 2012, 97 (2): 517-524. 10.1210/jc.2011-0618.CrossRefPubMed
33.
Guerra A, Fugazzola L, Marotta V, Cirillo M, Rossi S, Cirello V, Forno I, Moccia T, Budillon A, Vitale M: A high percentage of BRAFV600E alleles in papillary thyroid carcinoma predicts a poorer outcome. J Clin Endocrinol Metab. 2012, 97 (7): 2333-2340. 10.1210/jc.2011-3106.CrossRefPubMed
34.
Tiacci E, Trifonov V, Schiavoni G, Holmes A, Kern W, Martelli MP, Pucciarini A, Bigerna B, Pacini R, Wells VA: BRAF mutations in hairy-cell leukemia. N Engl J Med. 2011, 364 (24): 2305-2315. 10.1056/NEJMoa1014209.PubMedCentralCrossRefPubMed
35.
Xi L, Arons E, Navarro W, Calvo KR, Stetler-Stevenson M, Raffeld M, Kreitman RJ: Both variant and IGHV4-34-expressing hairy cell leukemia lack the BRAF V600E mutation. Blood. 2012, 119 (14): 3330-3332. 10.1182/blood-2011-09-379339.PubMedCentralCrossRefPubMed
36.
Morandi L, de Biase D, Visani M, Cesari V, De Maglio G, Pizzolitto S, Pession A, Tallini G: Allele Specific Locked Nucleic Acid Quantitative PCR (ASLNAqPCR): An Accurate and Cost-Effective Assay to Diagnose and Quantify KRAS and BRAF Mutation. PLoS One. 2012, 7 (4): e36084-10.1371/journal.pone.0036084.PubMedCentralCrossRefPubMed
37.
Lee HJ, Choi J, Hwang TS, Shong YK, Hong SJ, Gong G: Detection of BRAF mutations in thyroid nodules by allele-specific PCR using a dual priming oligonucleotide system. Am J Clin Pathol. 2010, 133 (5): 802-808. 10.1309/AJCPO3F2ENKMDTUS.CrossRefPubMed
38.
Jo YS, Huang S, Kim YJ, Lee IS, Kim SS, Kim JR, Oh T, Moon Y, An S, Ro HK: Diagnostic value of pyrosequencing for the BRAF V600E mutation in ultrasound-guided fine-needle aspiration biopsy samples of thyroid incidentalomas. Clin Endocrinol (Oxf). 2009, 70 (1): 139-144. 10.1111/j.1365-2265.2008.03293.x.CrossRef
39.
Dote H, Tsukuda K, Toyooka S, Yano M, Pass HI, Shimizu N: Mutation analysis of the BRAF codon 599 in malignant pleural mesothelioma by enriched PCR-RFLP. Oncol Rep. 2004, 11 (2): 361-363.PubMed
40.
Hayashida N, Namba H, Kumagai A, Hayashi T, Ohtsuru A, Ito M, Saenko VA, Maeda S, Kanematsu T, Yamashita S: A rapid and simple detection method for the BRAF(T1796A) mutation in fine-needle aspirated thyroid carcinoma cells. Thyroid. 2004, 14 (11): 910-915. 10.1089/thy.2004.14.910.CrossRefPubMed
41.
Benoit NE, Goldenberg D, Deng SX, Rosenbaum E, Cohen Y, Califano JA, Shackelford WH, Wang XB, Sidransky D: Colorimetric approach to high-throughput mutation analysis. Biotechniques. 2005, 38 (4): 635-639. 10.2144/05384PF01.CrossRefPubMed
42.
Lang AH, Drexel H, Geller-Rhomberg S, Stark N, Winder T, Geiger K, Muendlein A: Optimized allele-specific real-time PCR assays for the detection of common mutations in KRAS and BRAF. J Mol Diagn. 2011, 13 (1): 23-28. 10.1016/j.jmoldx.2010.11.007.PubMedCentralCrossRefPubMed
43.
Shinozaki M, O'Day SJ, Kitago M, Amersi F, Kuo C, Kim J, Wang HJ, Hoon DS: Utility of circulating B-RAF DNA mutation in serum for monitoring melanoma patients receiving biochemotherapy. Clin Cancer Res. 2007, 13 (7): 2068-2074. 10.1158/1078-0432.CCR-06-2120.PubMedCentralCrossRefPubMed
44.
Lee ST, Kim SW, Ki CS, Jang JH, Shin JH, Oh YL, Kim JW, Chung JH: Clinical implication of highly sensitive detection of the BRAF V600E mutation in fine-needle aspirations of thyroid nodules: a comparative analysis of three molecular assays in 4585 consecutive cases in a BRAF V600E mutation-prevalent area. J Clin Endocrinol Metab. 2012, 97 (7): 2299-2306. 10.1210/jc.2011-3135.CrossRefPubMed
45.
Eisen T, Ahmad T, Flaherty KT, Gore M, Kaye S, Marais R, Gibbens I, Hackett S, James M, Schuchter LM: Sorafenib in advanced melanoma: a Phase II randomised discontinuation trial analysis. Br J Cancer. 2006, 95 (5): 581-586. 10.1038/sj.bjc.6603291.PubMedCentralCrossRefPubMed
46.
Hauschild A, Agarwala SS, Trefzer U, Hogg D, Robert C, Hersey P, Eggermont A, Grabbe S, Gonzalez R, Gille J: Results of a phase III, randomized, placebo-controlled study of sorafenib in combination with carboplatin and paclitaxel as second-line treatment in patients with unresectable stage III or stage IV melanoma. J Clin Oncol. 2009, 27 (17): 2823-2830. 10.1200/JCO.2007.15.7636.CrossRefPubMed
47.
Kudo M, Ueshima K: Positioning of a molecular-targeted agent, sorafenib, in the treatment algorithm for hepatocellular carcinoma and implication of many complete remission cases in Japan. Oncology. 2010, 78 (Suppl 1): 154-166.CrossRefPubMed
48.
Stenner F, Chastonay R, Liewen H, Haile SR, Cathomas R, Rothermundt C, Siciliano RD, Stoll S, Knuth A, Buchler T: A pooled analysis of sequential therapies with sorafenib and sunitinib in metastatic renal cell carcinoma. Oncology. 2012, 82 (6): 333-340. 10.1159/000338001.CrossRefPubMed
49.
50.
Poulikakos PI, Zhang C, Bollag G, Shokat KM, Rosen N: RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF. Nature. 2010, 464 (7287): 427-430. 10.1038/nature08902.PubMedCentralCrossRefPubMed
51.
Yang H, Higgins B, Kolinsky K, Packman K, Bradley WD, Lee RJ, Schostack K, Simcox ME, Kopetz S, Heimbrook D: Antitumor activity of BRAF inhibitor vemurafenib in preclinical models of BRAF-mutant colorectal cancer. Cancer Res. 2012, 72 (3): 779-789. 10.1158/0008-5472.CAN-11-2941.CrossRefPubMed
52.
Hoeflich KP, Herter S, Tien J, Wong L, Berry L, Chan J, O'Brien C, Modrusan Z, Seshagiri S, Lackner M: Antitumor efficacy of the novel RAF inhibitor GDC-0879 is predicted by BRAFV600E mutational status and sustained extracellular signal-regulated kinase/mitogen-activated protein kinase pathway suppression. Cancer Res. 2009, 69 (7): 3042-3051. 10.1158/0008-5472.CAN-08-3563.CrossRefPubMed
53.
Stuart D, Li N, Poon DJ, Aardalen K, Kaufman S, Merritt H, Salangsang F, Lorenzana E, Li A, Ghoddusi M: Preclinical profile of LGX818: A potent and selective RAF kinase inhibitor. Cancer Res. 2012, 72 (Apr 25 supplement): 3790-CrossRef
54.
Schwartz G, Robertson S, Shen A, Wang E, Pace L, Dials H, Mendelson D, Shannon P, Gordon M: A phase I study of XL281, a selective oral RAF kinase inhibitor, in patients (Pts) with advanced solid tumors. J Clin Oncol. 2009, 27 (No. 15S (May 20 supplement)): 3513-
55.
Caronia LM, Phay JE, Shah MH: Role of BRAF in thyroid oncogenesis. Clin Cancer Res. 2011, 17 (24): 7511-7517. 10.1158/1078-0432.CCR-11-1155.CrossRefPubMed
56.
Yu Y, Zhao X, Gu X, Chang E, Cousens L, Chiesa E, Lowe D, Liu Y, Bul CO, Waghorne CG: Pharmacodynamic biomarkers for ARQ 736, a small molecule BRAF inhibitor. Cancer Res. 2010, 70 (8 Supplement of AACR 2010): 2517-CrossRef
57.
Wu C, Bekaii-Saab T: CpG Island Methylation, Microsatellite Instability, and BRAF Mutations and Their Clinical Application in the Treatment of Colon Cancer. Chemother Res Pract. 2012, 2012: 359041-PubMedCentralPubMed
58.
Jin N, Jiang T, Rosen DM, Nelkin BD, Ball DW: Synergistic action of a RAF inhibitor and a dual PI3K/mTOR inhibitor in thyroid cancer. Clin Cancer Res. 2011, 17 (20): 6482-6489. 10.1158/1078-0432.CCR-11-0933.CrossRefPubMed
59.
Sharfman WH, Hodi FS, Lawrence DP, Flaherty KT, Amaravadi RK, Kim KB, Dummer R, Gobbi S, Puzanov I, Sosman JA: Results from the first-in-human (FIH) phase I study of the oral RAF inhibitor RAF265 administered daily to patients with advanced cutaneous melanoma. ASCO Meeting Abstracts. 2011, 29 (15_suppl): 8508-
60.
Sosman JA, Kim KB, Schuchter L, Gonzalez R, Pavlick AC, Weber JS, McArthur GA, Hutson TE, Moschos SJ, Flaherty KT: Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med. 2012, 366 (8): 707-714. 10.1056/NEJMoa1112302.PubMedCentralCrossRefPubMed
61.
Hauschild A, Grob JJ, Demidov LV, Jouary T, Gutzmer R, Millward M, Rutkowski P, Blank CU, Miller WH, Kaempgen E: Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012, 380 (9839): 358-365. 10.1016/S0140-6736(12)60868-X.CrossRefPubMed
62.
Ponti G, Tomasi A, Pellacani G: Overwhelming response to Dabrafenib in a patient with double BRAF mutation (V600E; V600M) metastatic malignant melanoma. J Hematol Oncol. 2012, 5 (1): 60-10.1186/1756-8722-5-60.PubMedCentralCrossRefPubMed
63.
Long GV, Trefzer U, Davies MA, Kefford RF, Ascierto PA, Chapman PB, Puzanov I, Hauschild A, Robert C, Algazi A: Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, phase 2 trial. Lancet Oncol. 2012, 13 (11): 1087-1095. 10.1016/S1470-2045(12)70431-X.CrossRefPubMed
64.
Falchook GS, Long GV, Kurzrock R, Kim KB, Arkenau TH, Brown MP, Hamid O, Infante JR, Millward M, Pavlick AC: Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial. Lancet. 2012, 379 (9829): 1893-1901. 10.1016/S0140-6736(12)60398-5.PubMedCentralCrossRefPubMed
65.
Su F, Viros A, Milagre C, Trunzer K, Bollag G, Spleiss O, Reis-Filho JS, Kong X, Koya RC, Flaherty KT: RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med. 2012, 366 (3): 207-215. 10.1056/NEJMoa1105358.PubMedCentralCrossRefPubMed
66.
Joseph EW, Pratilas CA, Poulikakos PI, Tadi M, Wang W, Taylor BS, Halilovic E, Persaud Y, Xing F, Viale A: 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 (33): 14903-14908. 10.1073/pnas.1008990107.PubMedCentralCrossRefPubMed
67.
Solit DB, Garraway LA, Pratilas CA, Sawai A, Getz G, Basso A, Ye Q, Lobo JM, She Y, Osman I: BRAF mutation predicts sensitivity to MEK inhibition. Nature. 2006, 439 (7074): 358-362. 10.1038/nature04304.PubMedCentralCrossRefPubMed
68.
Fremin C, Meloche S: From basic research to clinical development of MEK1/2 inhibitors for cancer therapy. J Hematol Oncol. 2010, 3 (1): 8-10.1186/1756-8722-3-8.PubMedCentralCrossRefPubMed
69.
Wilmott JS, Long GV, Howle JR, Haydu LE, Sharma RN, Thompson JF, Kefford RF, Hersey P, Scolyer RA: Selective BRAF inhibitors induce marked T-cell infiltration into human metastatic melanoma. Clin Cancer Res. 2012, 18 (5): 1386-1394. 10.1158/1078-0432.CCR-11-2479.CrossRefPubMed
70.
Wu CP, Sim HM, Huang YH, Liu YC, Hsiao SH, Cheng HW, Li YQ, Ambudkar SV, Hsu SC: Overexpression of ATP-binding cassette transporter ABCG2 as a potential mechanism of acquired resistance to vemurafenib in BRAF(V600E) mutant cancer cells. Biochem Pharmacol. 2013, 85 (3): 325-334. 10.1016/j.bcp.2012.11.003.PubMedCentralCrossRefPubMed
71.
Villanueva J, Vultur A, Lee JT, Somasundaram R, Fukunaga-Kalabis M, Cipolla AK, Wubbenhorst B, Xu X, Gimotty PA, Kee D: Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R/PI3K. Cancer Cell. 2010, 18 (6): 683-695. 10.1016/j.ccr.2010.11.023.PubMedCentralCrossRefPubMed
72.
Nazarian R, Shi H, Wang Q, Kong X, Koya RC, Lee H, Chen Z, Lee MK, Attar N, Sazegar H: Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Nature. 2010, 468 (7326): 973-977. 10.1038/nature09626.PubMedCentralCrossRefPubMed
73.
Johannessen CM, Boehm JS, Kim SY, Thomas SR, Wardwell L, Johnson LA, Emery CM, Stransky N, Cogdill AP, Barretina J: COT drives resistance to RAF inhibition through MAP kinase pathway reactivation. Nature. 2010, 468 (7326): 968-972. 10.1038/nature09627.PubMedCentralCrossRefPubMed
74.
Poulikakos PI, Persaud Y, Janakiraman M, Kong X, Ng C, Moriceau G, Shi H, Atefi M, Titz B, Gabay MT: RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E). Nature. 2011, 480 (7377): 387-390. 10.1038/nature10662.PubMedCentralCrossRefPubMed
75.
Akinleye A, Furqan M, Mukhi N, Ravella P, Liu D: MEK and the inhibitors: from bench to bedside. J Hematol Oncol. 2013, 6 (1): 27-10.1186/1756-8722-6-27.PubMedCentralCrossRefPubMed
Metadata
Title
B-Raf and the inhibitors: from bench to bedside
Authors
Tiangui Huang
Michael Karsy
Jian Zhuge
Minghao Zhong
Delong Liu
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2013
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/1756-8722-6-30

Other articles of this Issue 1/2013

Journal of Hematology & Oncology 1/2013 Go to the issue

Review

MEK and the inhibitors: from bench to bedside

Review

The role of PD-1 and PD-L1 in T-cell immune suppression in patients with hematological malignancies

Research

Epigenetic inactivation of the MIR129-2 in hematological malignancies

Research

Detection of TP53 dysfunction in chronic lymphocytic leukemia by an in vitro functional assay based on TP53 activation by the non-genotoxic drug Nutlin-3: a proposal for clinical application

Research

Histone deacetylase inhibitor potentiated the ability of MTOR inhibitor to induce autophagic cell death in Burkitt leukemia/lymphoma

Research

Genomic amplification and high expression of EGFR are key targetable oncogenic events in malignant peripheral nerve sheath tumor
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits