RAS and BRAF in metastatic colorectal cancer management

被引:50
作者
Gong, Jun [1 ]
Cho, May [1 ]
Fakih, Marwan [2 ]
机构
[1] City Hope Natl Med Ctr, Dept Med Oncol, 1500 E Duarte Rd, Duarte, CA 91010 USA
[2] City Hope Comprehens Canc Ctr, Med Oncol & Expt Therapeut, Bldg 51,Room 127,1500 E Duarte St, Duarte, CA 91010 USA
关键词
RAS; BRAF; cetuximab; panitumumab; colorectal cancer (CRC);
D O I
10.21037/jgo.2016.06.12
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The treatment of metastatic colorectal cancer (mCRC) has been further refined with the development of monoclonal antibodies, cetuximab and panitumumab, towards the epidermal growth factor receptor (EGFR). Anti-EGFR therapy has afforded improved survival in those with wild-type RAS mCRC but provides no benefit and even harm in those with RAS-mutant tumors. BRAF mutations have also been shown to predict lack of clinically meaningful benefit to anti-EGFR therapy in mCRC. Mechanisms of resistance to EGFR blockade in wild-type RAS or BRAF metastatic colorectal tumors appear to converge on the mitogen-activated protein kinase (MAPK) signaling pathway. Clinical trials involving combined BRAF, EGFR, and/or MAPK kinase (MEK) inhibition have shown promising activity in BRAF-mutant mCRC. Here, we review pivotal clinical trials that have redefined our treatment approach in mCRC with respect to anti-EGFR therapy based on RAS and BRAF mutation status. Future studies will likely focus on improving efficacy of anti-EGFR-based therapy in mCRC through sustained MAPK pathway inhibition.
引用
收藏
页码:687 / 704
页数:18
相关论文
共 97 条
[1]   Clinical Acquired Resistance to RAF Inhibitor Combinations in BRAF-Mutant Colorectal Cancer through MAPK Pathway Alterations [J].
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. .
CANCER DISCOVERY, 2015, 5 (04) :358-367
[2]   American Society of Clinical Oncology Provisional Clinical Opinion: Testing for KRAS Gene Mutations in Patients With Metastatic Colorectal Carcinoma to Predict Response to Anti-Epidermal Growth Factor Receptor Monoclonal Antibody Therapy [J].
Allegra, Carmen J. ;
Jessup, J. Milburn ;
Somerfield, Mark R. ;
Hamilton, Stanley R. ;
Hammond, Elizabeth H. ;
Hayes, Daniel F. ;
McAllister, Pamela K. ;
Morton, Roscoe F. ;
Schilsky, Richard L. .
JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (12) :2091-2096
[3]   Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer [J].
Amado, Rafael G. ;
Wolf, Michael ;
Peeters, Marc ;
Van Cutsem, Eric ;
Siena, Salvatore ;
Freeman, Daniel J. ;
Juan, Todd ;
Sikorski, Robert ;
Suggs, Sid ;
Radinsky, Robert ;
Patterson, Scott D. ;
Chang, David D. .
JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (10) :1626-1634
[4]   Kirsten ras mutations in patients with colorectal cancer:: the 'RASCAL II' study [J].
Andreyev, HJN ;
Norman, AR ;
Cunningham, D ;
Oates, J ;
Dix, BR ;
Iacopetta, BJ ;
Young, J ;
Walsh, T ;
Ward, R ;
Hawkins, N ;
Beranek, M ;
Jandik, P ;
Benamouzig, R ;
Jullian, E ;
Laurent-Puig, P ;
Olschwang, S ;
Muller, O ;
Hoffmann, I ;
Rabes, HM ;
Zietz, C ;
Troungos, C ;
Valavanis, C ;
Yuen, ST ;
Ho, JWC ;
Croke, CT ;
O'Donoghue, DP ;
Giaretti, W ;
Rapallo, A ;
Russo, A ;
Bazan, V ;
Tanaka, M ;
Omura, K ;
Azuma, T ;
Ohkusa, T ;
Fujimori, T ;
Ono, Y ;
Pauly, M ;
Faber, C ;
Glaesener, R ;
de Goeij, AFPM ;
Arends, JW ;
Andersen, SN ;
Lövig, T ;
Breivik, J ;
Gaudernack, G ;
Clausen, OPF ;
De Angelis, P ;
Meling, GI ;
Rognum, TO ;
Smith, R .
BRITISH JOURNAL OF CANCER, 2001, 85 (05) :692-696
[5]   Kirsten ras mutations in patients with colorectal cancer: the multicenter "RASCAL" study [J].
Andreyev, HJN ;
Norman, AR ;
Cunningham, D ;
Oates, JR ;
Clarke, PA .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1998, 90 (09) :675-684
[6]   Updated efficacy of the MEK inhibitor trametinib (T), BRAF inhibitor dabrafenib (D), and anti-EGFR antibody panitumumab (P) in patients (pts) with BRAF V600E mutated (BRAFm) metastatic colorectal cancer (mCRC) [J].
Atreya, Chloe Evelyn ;
Van Cutsem, Eric ;
Bendell, Johanna C. ;
Andre, Thierry ;
Schellens, Jan H. M. ;
Gordon, Michael S. ;
McRee, Autumn Jackson ;
O'Dwyer, Peter J. ;
Muro, Kei ;
Tabernero, Josep ;
van Geel, Robin ;
Sidhu, Roger ;
Greger, James G. ;
Rangwala, Fatima A. ;
Motwani, Monica ;
Wu, Yuehui ;
Orford, Keith W. ;
Corcoran, Ryan Bruce .
JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (15)
[7]   Amplification of the MET Receptor Drives Resistance to Anti-EGFR Therapies in Colorectal Cancer [J].
Bardelli, Alberto ;
Corso, Simona ;
Bertotti, Andrea ;
Hobor, Sebastijan ;
Valtorta, Emanuele ;
Siravegna, Giulia ;
Sartore-Bianchi, Andrea ;
Scala, Elisa ;
Cassingena, Andrea ;
Zecchin, Davide ;
Apicella, Maria ;
Migliardi, Giorgia ;
Galimi, Francesco ;
Lauricella, Calogero ;
Zanon, Carlo ;
Perera, Timothy ;
Veronese, Silvio ;
Corti, Giorgio ;
Amatu, Alessio ;
Gambacorta, Marcello ;
Diaz, Luis A., Jr. ;
Sausen, Mark ;
Velculescu, Victor E. ;
Comoglio, Paolo ;
Trusolino, Livio ;
Di Nicolantonio, Federica ;
Giordano, Silvia ;
Siena, Salvatore .
CANCER DISCOVERY, 2013, 3 (06) :658-673
[8]   Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial [J].
Bennouna, Jaafar ;
Sastre, Javier ;
Arnold, Dirk ;
Osterlund, Pia ;
Greil, Richard ;
Van Cutsem, Eric ;
von Moos, Roger ;
Maria Vieitez, Jose ;
Bouche, Olivier ;
Borg, Christophe ;
Steffens, Claus-Christoph ;
Alonso-Orduna, Vicente ;
Schlichting, Christoph ;
Reyes-Rivera, Irmarie ;
Bendahmane, Belguendouz ;
Andre, Thierry ;
Kubicka, Stefan .
LANCET ONCOLOGY, 2013, 14 (01) :29-37
[9]   Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies [J].
Benvenuti, Silvia ;
Sartore-Bianchi, Andrea ;
Di Nicolantonio, Federica ;
Zanon, Carlo ;
Moroni, Mauro ;
Veronese, Silvio ;
Siena, Salvatore ;
Bardelli, Alberto .
CANCER RESEARCH, 2007, 67 (06) :2643-2648
[10]   The genomic landscape of response to EGFR blockade in colorectal cancer [J].
Bertotti, Andrea ;
Papp, Eniko ;
Jones, Sian ;
Adleff, Vilmos ;
Anagnostou, Valsamo ;
Lupo, Barbara ;
Sausen, Mark ;
Phallen, Jillian ;
Hruban, Carolyn A. ;
Tokheim, Collin ;
Niknafs, Noushin ;
Nesselbush, Monica ;
Lytle, Karli ;
Sassi, Francesco ;
Cottino, Francesca ;
Migliardi, Giorgia ;
Zanella, Eugenia R. ;
Ribero, Dario ;
Russolillo, Nadia ;
Mellano, Alfredo ;
Muratore, Andrea ;
Paraluppi, Gianluca ;
Salizzoni, Mauro ;
Marsoni, Silvia ;
Kragh, Michael ;
Lantto, Johan ;
Cassingena, Andrea ;
Li, Qing Kay ;
Karchin, Rachel ;
Scharpf, Robert ;
Sartore-Bianchi, Andrea ;
Siena, Salvatore ;
Diaz, Luis A., Jr. ;
Trusolino, Livio ;
Velculescu, Victor E. .
NATURE, 2015, 526 (7572) :263-+