Molecular Subtypes and Personalized Therapy in Metastatic Colorectal Cancer

被引:37
作者
Graham, Donna M. [1 ]
Coyle, Vicky M. [1 ]
Kennedy, Richard D. [1 ]
Wilson, Richard H. [1 ]
机构
[1] Queens Univ Belfast, Ctr Canc Res & Cell Biol, 97 Lisburn Rd, Belfast BT9 7AE, Antrim, North Ireland
关键词
Colorectal cancer; Biomarker stratification; Targeted therapy; Pathways; Molecular subtypes; Personalized medicine trials; Microsatellite instability; RAS; BRAF; EGFR; c-MET; HER2;
D O I
10.1007/s11888-016-0312-y
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Development of colorectal cancer occurs via a number of key pathways, with the clinicopathological features of specific subgroups being driven by underlying molecular changes. Mutations in key genes within the network of signalling pathways have been identified; however, therapeutic strategies to target these aberrations remain limited. As understanding of the biology of colorectal cancer has improved, this has led to a move toward broader genomic testing, collaborative research and innovative, adaptive clinical trial design. Recent developments in therapy include the routine adoption of wider mutational spectrum testing prior to use of targeted therapies and the first promise of effective immunotherapy for colorectal cancer patients. This review details current biomarkers in colorectal cancer for molecular stratification and for treatment allocation purposes, including open and planned precision medicine trials. Advances in our understanding, therapeutic strategy and technology will also be outlined.
引用
收藏
页码:141 / 150
页数:10
相关论文
共 83 条
[1]   The multifaceted roles of the receptor tyrosine kinase ROS in development and cancer [J].
Acquaviva, Jaime ;
Wong, Ricky ;
Charest, Al .
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2009, 1795 (01) :37-52
[2]   ROS1 and ALK Fusions in Colorectal Cancer, with Evidence of Intratumoral Heterogeneity for Molecular Drivers [J].
Aisner, Dara L. ;
Nguyen, Teresa T. ;
Paskulin, Diego D. ;
Le, Anh T. ;
Haney, Jerry ;
Schulte, Nathan ;
Chionh, Fiona ;
Hardingham, Jenny ;
Mariadason, John ;
Tebbutt, Niall ;
Doebele, Robert C. ;
Weickhardt, Andrew J. ;
Varella-Garcia, Marileila .
MOLECULAR CANCER RESEARCH, 2014, 12 (01) :111-118
[3]  
Boland CR, 2010, GASTROENTEROLOGY, V138, P2073, DOI [10.1053/j.gastro.2009.12.064, 10.1053/j.gastro.2010.04.024]
[4]   Gene expression patterns unveil a new level of molecular heterogeneity in colorectal cancer [J].
Budinska, Eva ;
Popovici, Vlad ;
Tejpar, Sabine ;
D'Ario, Giovanni ;
Lapique, Nicolas ;
Sikora, Katarzyna Otylia ;
Di Narzo, Antonio Fabio ;
Yan, Pu ;
Hodgson, John Graeme ;
Weinrich, Scott ;
Bosman, Fred ;
Roth, Arnaud ;
Delorenzi, Mauro .
JOURNAL OF PATHOLOGY, 2013, 231 (01) :63-76
[5]   Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study [J].
Camidge, D. Ross ;
Bang, Yung-Jue ;
Kwak, Eunice L. ;
Iafrate, A. John ;
Varella-Garcia, Marileila ;
Fox, Stephen B. ;
Riely, Gregory J. ;
Solomon, Benjamin ;
Ou, Sai-Hong I. ;
Kim, Dong-Wan ;
Salgia, Ravi ;
Fidias, Panagiotis ;
Engelman, Jeffrey A. ;
Gandhi, Leena ;
Jaenne, Pasi A. ;
Costa, Daniel B. ;
Shapiro, Geoffrey I. ;
LoRusso, Patricia ;
Ruffner, Katherine ;
Stephenson, Patricia ;
Tang, Yiyun ;
Wilner, Keith ;
Clark, Jeffrey W. ;
Shaw, Alice T. .
LANCET ONCOLOGY, 2012, 13 (10) :1011-1019
[6]   Characterization of the interactome of the human MutL homologues MLH1, PMS1, and PMS2 [J].
Cannavo, Elda ;
Gerrits, Bertran ;
Marra, Giancarlo ;
Schlapbach, Ralph ;
Jiricny, Josef .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (05) :2976-2986
[7]   Liquid biopsy: monitoring cancer-genetics in the blood [J].
Crowley, Emily ;
Di Nicolantonio, Federica ;
Loupakis, Fotios ;
Bardelli, Alberto .
NATURE REVIEWS CLINICAL ONCOLOGY, 2013, 10 (08) :472-484
[8]   KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer [J].
De Roock, Wendy ;
De Vriendt, Veerle ;
Normanno, Nicola ;
Ciardiello, Fortunato ;
Tejpar, Sabine .
LANCET ONCOLOGY, 2011, 12 (06) :594-603
[9]   Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis [J].
De Roock, Wendy ;
Claes, Bart ;
Bernasconi, David ;
De Schutter, Jef ;
Biesmans, Bart ;
Fountzilas, George ;
Kalogeras, Konstantine T. ;
Kotoula, Vassiliki ;
Papamichael, Demetris ;
Laurent-Puig, Pierre ;
Penault-Llorca, Frederique ;
Rougier, Philippe ;
Vincenzi, Bruno ;
Santini, Daniele ;
Tonini, Giuseppe ;
Cappuzzo, Federico ;
Frattini, Milo ;
Molinari, Francesca ;
Saletti, Piercarlo ;
De Dosso, Sara ;
Martini, Miriam ;
Bardelli, Alberto ;
Siena, Salvatore ;
Sartore-Bianchi, Andrea ;
Tabernero, Josep ;
Macarulla, Teresa ;
Di Fiore, Frederic ;
Gangloff, Alice Oden ;
Ciardiello, Fortunato ;
Pfeiffer, Per ;
Qvortrup, Camilla ;
Hansen, Tine Plato ;
Van Cutsem, Eric ;
Piessevaux, Hubert ;
Lambrechts, Diether ;
Delorenzi, Mauro ;
Tejpar, Sabine .
LANCET ONCOLOGY, 2010, 11 (08) :753-762
[10]  
Des Guetz G, 2010, ANTICANCER RES, V30, P4297