Predicting response to epidermal growth factor receptor-targeted therapy in colorectal cancer

Abstract

The discovery over 20 years ago by the Nobel Laureate Stanley Cohen of epidermal growth factor and its receptor, followed by the recognition that this receptor is overexpressed in multiple cancer types, has been of phenomenal significance. From these events the ‘Holy Grail’ of targeted therapy has looked increasingly realistic. Over the last 5 years this work has come of age with the licensing of multiple agents targeting this important mitogenic pathway in multiple tumor types. However, these agents and the technology behind them, while impressive, have resulted in lower clinical response rates than anticipated. In this review we will focus on the epidermal growth factor receptor-targeted therapies in colorectal cancer, why our expectations from these therapies have not yet been fulfilled and how we may predict those cancers that are likely to respond or be resistant to these therapies through a greater appreciation of the intricacy, diversity and dynamism of cellular signaling mechanisms.

Keywords::

• biological marker
• cetuximab
• colorectal cancer
• EGFR
• epidermal growth factor receptor
• erlotinib
• gefitinib
• panitumumab
• predictive marker
• targeted therapy

Notes

COX: Cyclooxygenase; K-Ras: Kirsten-ras; LOH: Loss of heterozygosity; pAkt: Phospho-Akt; PTEN: Phosphatases and tensin homolog; uPAr: Urokinase plasminogen activator receptor.