KRAS mutations and sensitivity to anti-EGFR monoclonal antibodies in metastatic colorectal carcinoma: an open issue.

Antonio Russo, Evaristo Maiello, Stefania Tommasi, Nicola Silvestris, Giuseppe Colucci, Gianni Simone, Giuseppe Tonini, Daniele Santini, Daniela Petriella

Risultato della ricerca: Article

11 Citazioni (Scopus)

Abstract

Background: Cetuximab and panitumumab, mAbs targeting EGFR, are registered for metastatic colorectal carcinoma (mCRC) patients whose tumors express EGFR as determined by immunohistochemistry. However, this method is not predictive of treatment efficacy. KRAS, the human homolog of the Kirsten rat sarcoma-2 virus oncogene, encodes a small G-protein that functions downstream of EGFR-induced signalling. Objective/Methods: To examine KRAS mutations as predictive factors of response to anti-EGFR mAbs using recently published data. Results/conclusions: Several retrospective studies show that efficacy of these mAbs is confined to patients with wild type KRAS and genotyping of tumors should be considered before treatment. The absence of KRAS mutations does not guarantee an improved likelihood of response to cetuximab and panitumumab. Investigation of other genetic and epigenetic biomarkers will be useful to further refine the responder population. Prospective studies to test the efficacy of combined therapies simultaneously targeting EGFR and the RAS/RAF/MAPK signalling pathways for mCRC are warranted.
Lingua originaleEnglish
pagine (da-a)565-577
Numero di pagine13
RivistaExpert Opinion on Pharmacotherapy
Volume9(5):
Stato di pubblicazionePublished - 2009

Fingerprint

Tumors
Colorectal Neoplasms
Monoclonal Antibodies
Mutation
Monomeric GTP-Binding Proteins
Biomarkers
Viruses
Oncogenes
Epigenomics
Sarcoma
Rats
Neoplasms
Retrospective Studies
Immunohistochemistry
Prospective Studies
Therapeutics
Population
panitumumab
Cetuximab

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Clinical Biochemistry
  • Drug Discovery

Cita questo

Russo, A., Maiello, E., Tommasi, S., Silvestris, N., Colucci, G., Simone, G., ... Petriella, D. (2009). KRAS mutations and sensitivity to anti-EGFR monoclonal antibodies in metastatic colorectal carcinoma: an open issue. Expert Opinion on Pharmacotherapy, 9(5):, 565-577.

KRAS mutations and sensitivity to anti-EGFR monoclonal antibodies in metastatic colorectal carcinoma: an open issue. / Russo, Antonio; Maiello, Evaristo; Tommasi, Stefania; Silvestris, Nicola; Colucci, Giuseppe; Simone, Gianni; Tonini, Giuseppe; Santini, Daniele; Petriella, Daniela.

In: Expert Opinion on Pharmacotherapy, Vol. 9(5):, 2009, pag. 565-577.

Risultato della ricerca: Article

Russo, A, Maiello, E, Tommasi, S, Silvestris, N, Colucci, G, Simone, G, Tonini, G, Santini, D & Petriella, D 2009, 'KRAS mutations and sensitivity to anti-EGFR monoclonal antibodies in metastatic colorectal carcinoma: an open issue.', Expert Opinion on Pharmacotherapy, vol. 9(5):, pagg. 565-577.
Russo, Antonio ; Maiello, Evaristo ; Tommasi, Stefania ; Silvestris, Nicola ; Colucci, Giuseppe ; Simone, Gianni ; Tonini, Giuseppe ; Santini, Daniele ; Petriella, Daniela. / KRAS mutations and sensitivity to anti-EGFR monoclonal antibodies in metastatic colorectal carcinoma: an open issue. In: Expert Opinion on Pharmacotherapy. 2009 ; Vol. 9(5):. pagg. 565-577.
@article{9fdcbe9dee9e4e4eaffab8aa6aae2c3c,
title = "KRAS mutations and sensitivity to anti-EGFR monoclonal antibodies in metastatic colorectal carcinoma: an open issue.",
abstract = "Background: Cetuximab and panitumumab, mAbs targeting EGFR, are registered for metastatic colorectal carcinoma (mCRC) patients whose tumors express EGFR as determined by immunohistochemistry. However, this method is not predictive of treatment efficacy. KRAS, the human homolog of the Kirsten rat sarcoma-2 virus oncogene, encodes a small G-protein that functions downstream of EGFR-induced signalling. Objective/Methods: To examine KRAS mutations as predictive factors of response to anti-EGFR mAbs using recently published data. Results/conclusions: Several retrospective studies show that efficacy of these mAbs is confined to patients with wild type KRAS and genotyping of tumors should be considered before treatment. The absence of KRAS mutations does not guarantee an improved likelihood of response to cetuximab and panitumumab. Investigation of other genetic and epigenetic biomarkers will be useful to further refine the responder population. Prospective studies to test the efficacy of combined therapies simultaneously targeting EGFR and the RAS/RAF/MAPK signalling pathways for mCRC are warranted.",
keywords = "KRAS,colorectal carcinoma",
author = "Antonio Russo and Evaristo Maiello and Stefania Tommasi and Nicola Silvestris and Giuseppe Colucci and Gianni Simone and Giuseppe Tonini and Daniele Santini and Daniela Petriella",
year = "2009",
language = "English",
volume = "9(5):",
pages = "565--577",
journal = "Expert Opinion on Pharmacotherapy",
issn = "1465-6566",
publisher = "Informa Healthcare",

}

TY - JOUR

T1 - KRAS mutations and sensitivity to anti-EGFR monoclonal antibodies in metastatic colorectal carcinoma: an open issue.

AU - Russo, Antonio

AU - Maiello, Evaristo

AU - Tommasi, Stefania

AU - Silvestris, Nicola

AU - Colucci, Giuseppe

AU - Simone, Gianni

AU - Tonini, Giuseppe

AU - Santini, Daniele

AU - Petriella, Daniela

PY - 2009

Y1 - 2009

N2 - Background: Cetuximab and panitumumab, mAbs targeting EGFR, are registered for metastatic colorectal carcinoma (mCRC) patients whose tumors express EGFR as determined by immunohistochemistry. However, this method is not predictive of treatment efficacy. KRAS, the human homolog of the Kirsten rat sarcoma-2 virus oncogene, encodes a small G-protein that functions downstream of EGFR-induced signalling. Objective/Methods: To examine KRAS mutations as predictive factors of response to anti-EGFR mAbs using recently published data. Results/conclusions: Several retrospective studies show that efficacy of these mAbs is confined to patients with wild type KRAS and genotyping of tumors should be considered before treatment. The absence of KRAS mutations does not guarantee an improved likelihood of response to cetuximab and panitumumab. Investigation of other genetic and epigenetic biomarkers will be useful to further refine the responder population. Prospective studies to test the efficacy of combined therapies simultaneously targeting EGFR and the RAS/RAF/MAPK signalling pathways for mCRC are warranted.

AB - Background: Cetuximab and panitumumab, mAbs targeting EGFR, are registered for metastatic colorectal carcinoma (mCRC) patients whose tumors express EGFR as determined by immunohistochemistry. However, this method is not predictive of treatment efficacy. KRAS, the human homolog of the Kirsten rat sarcoma-2 virus oncogene, encodes a small G-protein that functions downstream of EGFR-induced signalling. Objective/Methods: To examine KRAS mutations as predictive factors of response to anti-EGFR mAbs using recently published data. Results/conclusions: Several retrospective studies show that efficacy of these mAbs is confined to patients with wild type KRAS and genotyping of tumors should be considered before treatment. The absence of KRAS mutations does not guarantee an improved likelihood of response to cetuximab and panitumumab. Investigation of other genetic and epigenetic biomarkers will be useful to further refine the responder population. Prospective studies to test the efficacy of combined therapies simultaneously targeting EGFR and the RAS/RAF/MAPK signalling pathways for mCRC are warranted.

KW - KRAS,colorectal carcinoma

UR - http://hdl.handle.net/10447/42698

M3 - Article

VL - 9(5):

SP - 565

EP - 577

JO - Expert Opinion on Pharmacotherapy

JF - Expert Opinion on Pharmacotherapy

SN - 1465-6566

ER -