Only approximately 10 % of genetically unselected patients with chemorefractory metastatic colorectal cancer experience tumor regression when treated with the anti-epidermal growth factor receptor (EGFR) antibodies cetuximab or panitumumab ("primary" or "de novo" resistance). Moreover, nearly all patients whose tumors initially respond inevitably become refractory ("secondary" or "acquired" resistance). An ever-increasing number of predictors of both primary and acquired resistance to anti-EGFR antibodies have been described, and it is now evident that most of the underlying mechanisms significantly overlap. By trying to extrapolate a unifying perspective out of many idiosyncratic details, here, we discuss the molecular underpinnings of therapeutic resistance, summarize research efforts aimed to improve patient selection, and present alternative therapeutic strategies that are now under development to increase response and combat relapse.

Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies.

LETO, SIMONETTA MARIA;TRUSOLINO, Livio
2014

Abstract

Only approximately 10 % of genetically unselected patients with chemorefractory metastatic colorectal cancer experience tumor regression when treated with the anti-epidermal growth factor receptor (EGFR) antibodies cetuximab or panitumumab ("primary" or "de novo" resistance). Moreover, nearly all patients whose tumors initially respond inevitably become refractory ("secondary" or "acquired" resistance). An ever-increasing number of predictors of both primary and acquired resistance to anti-EGFR antibodies have been described, and it is now evident that most of the underlying mechanisms significantly overlap. By trying to extrapolate a unifying perspective out of many idiosyncratic details, here, we discuss the molecular underpinnings of therapeutic resistance, summarize research efforts aimed to improve patient selection, and present alternative therapeutic strategies that are now under development to increase response and combat relapse.
92
7
709
722
http://link.springer.com/article/10.1007%2Fs00109-014-1161-2
Colorectal cancer; Targeted therapy; Anti-EGFR antibodies; Primary resistance; Secondary resistance; Response biomarkers
Leto SM;Trusolino L
File in questo prodotto:
File Dimensione Formato  
Primary and acquired resistance to EGFR.pdf

Accesso aperto con embargo fino al 15/07/2015

Tipo di file: POSTPRINT (VERSIONE FINALE DELL’AUTORE)
Dimensione 425.18 kB
Formato Adobe PDF
425.18 kB Adobe PDF Visualizza/Apri
2014_Primary and acquired resistance to EGFR-targeted therapies.pdf

Accesso riservato

Tipo di file: PDF EDITORIALE
Dimensione 1.1 MB
Formato Adobe PDF
1.1 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/149162
Citazioni
  • ???jsp.display-item.citation.pmc??? 32
  • Scopus 63
  • ???jsp.display-item.citation.isi??? 61
social impact