Precision medicine in colorectal cancer: the molecular profile alters treatment strategies.
When considering treatment options for patients with metastatic colorectal cancer (mCRC), molecular profiling has become a pivotal component in guiding clinical decisions. FOLFOX and FOLFIRI (fluorouracuil, leucovorin plus oxaliplatin or ininotecan, respectively) are the standard base regimens used for the treatment of mCRC. Biologic agents, such as the epidermal growth factor receptor (EGFR) targeted therapies, cetuximab and panitumumab and the vascular endothelial growth factor monoclonal antibody, bevacizumab, are safe and effective in the first-line setting. The most efficacious use of these agents in terms of timing and selection of the right patient population continues to be debated. Here we review multiple investigations into the effectiveness of treatment options as a function of the mutations present in colon cancers. Early studies have reported thatKRASmutations at exon 2 predict resistance to EGFR targeted therapies. More recently the data have expanded to includeKRASmutations at exons 3 and 4 andNRASmutations at exons 2, 3 and 4 as well as other biomarkers includingBRAFandPIK3CA, leading to the evolution of the treatment of mCRC to a more precision-based approach. As our understanding of relevant biomarkers increases, and data from both molecular profiling and treatment response become more readily available, treatment options will become more precise and their outcomes more effective.
Division of Hematology and Oncology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.
Nguyen H
NH
Tran
Division of Hematology and Oncology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, and University of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Ludimila L
LL
Cavalcante
Division of Hematology and Oncology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, and University of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Sam J
SJ
Lubner
Division of Hematology and Oncology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, and University of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Daniel L
DL
Mulkerin
Division of Hematology and Oncology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, and University of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Noelle K
NK
LoConte
Department of Oncology, University of Wisconsin-Madison, Madison, WI, USA.
Linda
L
Clipson
University of Wisconsin Carbone Cancer Center, and Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison School of Medicine and Public Health, and William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.
Kristina A
KA
Matkowskyj
Division of Hematology and Oncology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, 600 Highland Avenue, K6/544, Madison, WI 53792, USA.
Dustin A
DA
Deming
BRAF; KRAS; NRAS; PIK3CA; cetuximab; panitumumab