Novel drug discovery opportunities for colorectal cancer.

Introduction: Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide, with > 1.2 million new cases and > 600,000 deaths per year. This complex disease is driven by multiple genetic lesions, commonly dysregulated signaling pathways, and aberrant activity of developmental programs such as Notch and Wnt. While emerging therapies such as EGFR inhibitors are improving treatment regimens, recent findings elucidating the role of cancer stem cells provide insights into opportunities for novel therapeutic intervention.

Areas Covered: This review provides a background on CRC statistics, colon anatomy and CRC pathobiology, CRC genetics and current and emerging therapies. Furthermore, the article discusses the role of developmental signaling pathways governing self-renewal biology as potential points for therapeutic intervention.

Expert Opinion: Despite recent advances including the introduction of targeted therapeutics, prognosis for advanced CRC patients remains bleak, reinforcing the need for novel therapeutic intervention. Developmental pathways such as Notch and Wnt provide opportunities to address this urgent need, and preclinical evidence supports targeting these pathways in CRC. Progress has been made toward this end, and while challenges persist, an increasing number of preclinical findings show promise.