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Selecting the best targeted agent in first-line treatment of unresectable liver metastases from colorectal cancer: does the bench have the answers?

  • Topics
  • Therapeutic strategies for hepatic metastasis of colorectal cancer: 2011 Update
  • Published:
Journal of Hepato-Biliary-Pancreatic Sciences

Abstract

For physicians facing patients with organ-limited metastases from colorectal cancer, tumor shrinkage and sterilization of micrometastatic disease is the main goal, giving the opportunity for secondary surgical resection. At the same time, for the majority of patients who will not achieve a sufficient tumor response, disease control remains the predominant objective. Since FOLFOX or FOLFIRI have similar efficacies, the challenge is to define which could be the most effective targeted agent (anti-EGFR or anti-VEGF) to reach these goals. Therefore, a priori molecular identification of patients that could benefit from anti-EGFR or anti-VEGF monoclonal antibodies (i.e. the currently approved targeted therapies for metastatic colorectal cancer) is of critical importance. In this setting, the KRAS mutation status was the first identified predictive marker of response to anti-EGFR therapy. Since it has been demonstrated that tumors with KRAS mutation do not respond to anti-EGFR therapy, KRAS status must be determined prior to treatment. Thus, for KRAS wild-type patients, the choices that remain are either anti-VEGF or anti-EGFR. In this review, we present the most updated data from translational research programs dealing with the identification of biomarkers for response to targeted therapies.

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Abbreviations

AKT:

v-akt murine thymoma viral oncogene homolog

AREG:

Amphiregulin

CCND1:

Cyclin D1

CI:

Confidence interval

COX2:

Cyclooxygenase-2

CXCR:

Chemokine receptor

EGFRs:

Epidermal growth factor receptor

EREG:

Epiregulin

ERK:

Extracellular signal-regulated kinases

ELISA:

Enzyme-linked immunosorbent assay

FcνR:

Immunoglobulin-G fragment-C receptors

FOLFIRI:

5-Fluorouracil (5-FU)/irinotecan

FOLFOX:

5-Fluorouracil (5-FU)/leucovorin with oxaliplatin

HER:

Epidermal growth factor receptor

HR:

Hazard ratio

IFL:

Irinotecan, leucovorin (folinic acid), and fluorouracil

IGF1:

Insulin-like growth factor 1

IGF1R:

Insulin-like growth factor receptor 1

IHC:

Immunohistochemistry

Il-8:

Interleukin 8

KRAS:

Kirsten rat sarcoma viral oncogene homolog

KRAS-M:

KRAS mutated tumor

KRAS-WT:

KRAS wild-type tumors

Lcs6:

Binding site for the let-7

Let 7:

Lethal-7

mBC:

Metastatic breast cancer

mCRC:

Metastatic colorectal cancer

MEK:

Mitogen-activated protein kinase

mL:

Milliliter

MoAB:

Monoclonal antibody

mRNA:

Messenger ribonucleic acid

miRNA:

Micro ribonucleic acid

MoAb:

Monoclonal antibody

mTOR:

Mammalian target of rapamycin

NRP:

Neurophilin

OR:

Odd ratio

OS:

Overall survival

pg:

Picogram

PTEN:

Phosphatase and tensin homolog

PI3K:

Phosphoinositide 3-kinase

PIP:

Prolactin-induced protein

PFS:

Progression-free survival

RAF:

Murine sarcoma viral oncogene downstream of the Ras subfamily

RAS:

Rat sarcoma

RR:

Response rate

SNPs:

Single nucleotide polymorphisms

TGF:

Transforming growth factor

UTR:

Untranslated region

VEGF:

Vascular endothelial growth factor

VEGFR:

Vascular endothelial growth factor receptor

XELOX:

Capecitabine and oxaliplatin

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Authors and Affiliations

  1. Division of Medical Oncology, USC Norris Comprehensive Cancer Center, Los Angeles, CA Doctoral Research Fellow Keck School of Medicine, 1441 Eastlake Avenue, NOR 5410, Los Angeles, CA, 90033, USA

    L. Benhaim, F. Loupakis, M. J. LaBonte & H. J. Lenz

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  1. L. Benhaim
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  2. F. Loupakis
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  3. M. J. LaBonte
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  4. H. J. Lenz
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Correspondence to L. Benhaim.

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Benhaim, L., Loupakis, F., LaBonte, M.J. et al. Selecting the best targeted agent in first-line treatment of unresectable liver metastases from colorectal cancer: does the bench have the answers?. J Hepatobiliary Pancreat Sci 19, 528–535 (2012). https://doi.org/10.1007/s00534-012-0526-6

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  • DOI: https://doi.org/10.1007/s00534-012-0526-6

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