BRAF in metastatic colorectal cancer: the future starts now

被引：14
作者：
Orlandi, Armando [1 ]
Calegari, Maria Alessandra [1 ]
Inno, Alessandro [2 ]
Berenato, Rosa [3 ]
Caporale, Marta [3 ]
Niger, Monica [3 ]
Bossi, Ilaria [3 ]
Di Bartolomeo, Maria [3 ]
de Braud, Filippo [3 ]
Pietrantonio, Filippo [3 ]
机构：
[1] Univ Cattolica Sacro Cuore, Dept Med Oncol, Rome, Italy
[2] Sacro Cuore Don Calabria Hosp, Med Oncol, Verona, Italy
[3] Fdn IRCCS Ist Nazl Tumori, Dept Med Oncol, Milan, Italy
来源：
PHARMACOGENOMICS | 2015年 / 16卷 / 18期
关键词：
BRAF; colorectal cancer; immunotherapy; target therapy; FOLFOXIRI PLUS BEVACIZUMAB; EGFR MONOCLONAL-ANTIBODIES; KRAS MUTATIONAL STATUS; COLON-CANCER; V600E MUTATION; MICROSATELLITE INSTABILITY; 1ST-LINE TREATMENT; RAS MUTATIONS; POOR SURVIVAL; MAPK PATHWAY;
D O I：
10.2217/pgs.15.140
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
BRAF mutations are detectable in about 5-15% of metastatic colorectal cancer (mCRC) patients and represent a clear negative prognostic factor. While in BRAF-mutated (BRAFmt) metastatic melanoma TKI target therapies (BRAF and MEK inhibitor), both alone or in combination, have shown significant efficacy, in BRAFmt CRC single-agent BRAF-inhibitors as well as chemotherapy seem to be ineffective. The critical role of EGFR in CRC and its multiple downstreaming pathways seem to be involved in this lack of response. In recent years, preclinical investigations and retrospective studies slowly increased our knowledge on BRAFmt CRC. This review analyses preclinical data and discusses several clinical trials in order to explore new therapeutic strategies targeting BRAFmt mCRC.
引用
收藏
页码：2069 / 2081
页数：13
相关论文
共 65 条
  • [1] Clinical Acquired Resistance to RAF Inhibitor Combinations in BRAF-Mutant Colorectal Cancer through MAPK Pathway Alterations
    Ahronian, Leanne G.
    Sennott, Erin M.
    Van Allen, Eliezer M.
    Wagle, Nikhil
    Kwak, Eunice L.
    Faris, Jason E.
    Godfrey, Jason T.
    Nishimura, Koki
    Lynch, Kerry D.
    Mermel, Craig H.
    Lockerman, Elizabeth L.
    Kalsy, Anuj
    Gurski, Joseph M., Jr.
    Bahl, Samira
    Anderka, Kristin
    Green, Lisa M.
    Lennon, Niall J.
    Huynh, Tiffany G.
    Mino-Kenudson, Mari
    Getz, Gad
    Dias-Santagata, Dora
    Iafrate, A. John
    Engelman, Jeffrey A.
    Garraway, Levi A.
    Corcoran, Ryan B.
    [J]. CANCER DISCOVERY, 2015, 5 (04) : 358 - 367
  • [2] [Anonymous], 2015, J CLIN ONCOL, DOI DOI 10.1158/2159-8290.CD-16-0050
  • [3] KRAS mutational status affects oxaliplatin-based chemotherapy independently from basal mRNA ERCC-1 expression in metastatic colorectal cancer patients
    Basso, M.
    Strippoli, A.
    Orlandi, A.
    Martini, M.
    Calegari, M. A.
    Schinzari, G.
    Di Salvatore, M.
    Cenci, T.
    Cassano, A.
    Larocca, L. M.
    Barone, C.
    [J]. BRITISH JOURNAL OF CANCER, 2013, 108 (01) : 115 - 120
  • [4] Bendell JC, 2014, J CLIN ONCOL S5S, V32
  • [5] Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: Pooled analysis of the CRYSTAL and OPUS randomised clinical trials
    Bokemeyer, Carsten
    Van Cutsem, Eric
    Rougier, Philippe
    Ciardiello, Fortunato
    Heeger, Steffen
    Schlichting, Michael
    Celik, Ilhan
    Koehne, Claus-Henning
    [J]. EUROPEAN JOURNAL OF CANCER, 2012, 48 (10) : 1466 - 1475
  • [6] Assessment of BRAF V600E mutation status by immunohistochemistry with a mutation-specific monoclonal antibody
    Capper, David
    Preusser, Matthias
    Habel, Antje
    Sahm, Felix
    Ackermann, Ulrike
    Schindler, Genevieve
    Pusch, Stefan
    Mechtersheimer, Gunhild
    Zentgraf, Hanswalter
    von Deimling, Andreas
    [J]. ACTA NEUROPATHOLOGICA, 2011, 122 (01) : 11 - 19
  • [7] Mammalian MAP kinase signalling cascades
    Chang, LF
    Karin, M
    [J]. NATURE, 2001, 410 (6824) : 37 - 40
  • [8] Mechanisms of regulating the Raf kinase family
    Chong, H
    Vikis, HG
    Guan, KL
    [J]. CELLULAR SIGNALLING, 2003, 15 (05) : 463 - 469
  • [9] EGFR-Mediated Reactivation of MAPK Signaling Contributes to Insensitivity of BRAF-Mutant Colorectal Cancers to RAF Inhibition with Vemurafenib
    Corcoran, Ryan B.
    Ebi, Hiromichi
    Turke, Alexa B.
    Coffee, Erin M.
    Nishino, Michiya
    Cogdill, Alexandria P.
    Brown, Ronald D.
    Della Pelle, Patricia
    Dias-Santagata, Dora
    Hung, Kenneth E.
    Flaherty, Keith T.
    Piris, Adriano
    Wargo, Jennifer A.
    Settleman, Jeffrey
    Mino-Kenudson, Mari
    Engelman, Jeffrey A.
    [J]. CANCER DISCOVERY, 2012, 2 (03) : 227 - 235
  • [10] BRAF codons 594 and 596 mutations identify a new molecular subtype of metastatic colorectal cancer at favorable prognosis
    Cremolini, C.
    Di Bartolomeo, M.
    Amatu, A.
    Antoniotti, C.
    Moretto, R.
    Berenato, R.
    Perrone, F.
    Tamborini, E.
    Aprile, G.
    Lonardi, S.
    Sartore-Bianchi, A.
    Fontanini, G.
    Milione, M.
    Lauricella, C.
    Siena, S.
    Falcone, A.
    de Braud, F.
    Loupakis, F.
    Pietrantonio, F.
    [J]. ANNALS OF ONCOLOGY, 2015, 26 (10) : 2092 - 2097
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