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109. Rahman MA et al (2014) BRAF inhibitors: from the laboratory to clinical trials. Crit Rev
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110. Alcala AM, Flaherty KT (2012) BRAF inhibitors for the treatment of metastatic melanoma:
clinical trials and mechanisms of resistance. Clin Cancer Res 18(1):33–39
111. Bollag G et al (2010) Clinical efficacy of a RAF inhibitor needs broad target blockade in
BRAF-mutant melanoma. Nature 467(7315):596–599
112. Tap WD et al (2010) Pharmacodynamic characterization of the efficacy signals due to selective
BRAF inhibition with PLX4032 in malignant melanoma. Neoplasia 12(8):637–649
113. Chapman PB et al (2011) Improved survival with vemurafenib in melanoma with BRAF
V600E mutation. N Engl J Med 364(26):2507–2516
114. da Rocha Dias S et al (2013) The European Medicines Agency review of vemurafenib
(Zelboraf(R)) for the treatment of adult patients with BRAF V600 mutation-positive
Exploiting Kinase Inhibitors for Cancer Treatment: An Overview of Clinical. . .
149
kinase by ATP-site and myristoyl pocket inhibitors. Proc Natl Acad Sci 110(47):E4437–
E4445
92. Shah NP et al (2004) Overriding imatinib resistance with a novel ABL kinase inhibitor.
Science 305(5682):399–401
93. Boschelli DH et al (2001) Optimization of 4-Phenylamino-3-quinolinecarbonitriles as potent
inhibitors of Src kinase activity. J Med Chem 44(23):3965–3977
94. Boschelli F, Arndt K, Gambacorti-Passerini C (2010) Bosutinib: a review of preclinical studies
in chronic myelogenous leukaemia. Eur J Cancer 46(10):1781–1789
95. Redaelli S et al (2009) Activity of bosutinib, dasatinib, and nilotinib against 18 imatinibresistant BCR/ABL mutants. J Clin Oncol 27(3):469–471
96. Cortes JE et al (2017) Bosutinib versus imatinib for newly diagnosed chronic myeloid
leukemia: results from the randomized BFORE trial. J Clin Oncol 36(3):231–237
97. Huang W-S et al (2010) Discovery of 3-[2-(Imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methylN-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a
potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase
including the T315I gatekeeper mutant. J Med Chem 53(12):4701–4719
98. Cortes JE et al (2012) Ponatinib in refractory Philadelphia chromosome–positive leukemias.
N Engl J Med 367(22):2075–2088
99. Nicolini FE et al (2015) The impact of ponatinib versus allogeneic stem cell transplant (SCT)
on outcomes in patients with chronic myeloid leukemia (CML) or Philadelphia chromosomepositive acute lymphoblastic leukemia (Ph+ ALL) with the T315I mutation. Blood 126
(23):480–480
100. Samatar AA, Poulikakos PI (2014) Targeting RAS-ERK signalling in cancer: promises and
challenges. Nat Rev Drug Discov 13(12):928–942
101. Agianian B, Gavathiotis E (2018) Current insights of BRAF inhibitors in cancer. J Med Chem
61(14):5775–5793
102. Lavoie H, Therrien M (2015) Regulation of RAF protein kinases in ERK signalling. Nat Rev
Mol Cell Biol 16(5):281–298
103. Roring M et al (2012) Distinct requirement for an intact dimer interface in wild-type, V600E
and kinase-dead B-Raf signalling. EMBO J 31(11):2629–2647
104. Rajakulendran T et al (2009) A dimerization-dependent mechanism drives RAF catalytic
activation. Nature 461(7263):542–545
105. Heidorn SJ et al (2010) Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor
progression through CRAF. Cell 140(2):209–221
106. Davies H et al (2002) Mutations of the BRAF gene in human cancer. Nature 417
(6892):949–954
107. Schubbert S, Shannon K, Bollag G (2007) Hyperactive Ras in developmental disorders and
cancer. Nat Rev Cancer 7(4):295–308
108. Zambon A et al (2012) Small molecule inhibitors of BRAF in clinical trials. Bioorg Med Chem
Lett 22(2):789–792
109. Rahman MA et al (2014) BRAF inhibitors: from the laboratory to clinical trials. Crit Rev
Oncol Hematol 90(3):220–232
110. Alcala AM, Flaherty KT (2012) BRAF inhibitors for the treatment of metastatic melanoma:
clinical trials and mechanisms of resistance. Clin Cancer Res 18(1):33–39
111. Bollag G et al (2010) Clinical efficacy of a RAF inhibitor needs broad target blockade in
BRAF-mutant melanoma. Nature 467(7315):596–599
112. Tap WD et al (2010) Pharmacodynamic characterization of the efficacy signals due to selective
BRAF inhibition with PLX4032 in malignant melanoma. Neoplasia 12(8):637–649
113. Chapman PB et al (2011) Improved survival with vemurafenib in melanoma with BRAF
V600E mutation. N Engl J Med 364(26):2507–2516
114. da Rocha Dias S et al (2013) The European Medicines Agency review of vemurafenib
(Zelboraf(R)) for the treatment of adult patients with BRAF V600 mutation-positive
Exploiting Kinase Inhibitors for Cancer Treatment: An Overview of Clinical. . .
149