Oncology Drug Discovery, Research and Development, Bristol-Myers Squibb, Route 206 and Provinceline Road, Princeton, NJ, USA.
Expert Opin Drug Discov. 2013 Sep;8(9):1153-64. doi: 10.1517/17460441.2013.807249. Epub 2013 Jun 17.
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.
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.
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.
结直肠癌（CRC）是全球癌症死亡的主要原因，每年有超过 120 万例新发病例和超过 60 万例死亡。这种复杂的疾病是由多种遗传损伤、常见的信号通路失调以及 Notch 和 Wnt 等发育程序的异常活性驱动的。尽管新兴的治疗方法，如 EGFR 抑制剂，正在改善治疗方案，但最近阐明癌症干细胞作用的发现为新的治疗干预提供了机会。
这篇综述提供了结直肠癌统计数据、结肠解剖结构和 CRC 病理生物学、CRC 遗传学以及当前和新兴治疗方法的背景。此外，文章还讨论了发育信号通路在自我更新生物学中的作用，作为潜在的治疗干预点。
尽管最近取得了进展，包括引入靶向治疗，但晚期 CRC 患者的预后仍然不容乐观，这加剧了对新的治疗干预的需求。发育途径，如 Notch 和 Wnt，为满足这一迫切需求提供了机会，并且临床前证据支持在 CRC 中靶向这些途径。已经为此取得了进展，尽管仍然存在挑战，但越来越多的临床前发现显示出了希望。
