Oncologia Medica and Immunologia Clinica, Dipartimento Medico-Chirurgico di Internistica Clinica e Sperimentale F. Magrassi e A. Lanzara, Seconda Università degli Studi di Napoli, Napoli, Italy.
Ther Adv Med Oncol. 2013 Jan;5(1):51-72. doi: 10.1177/1758834012462462.
The prognosis of patients with cancer remains poor in spite of the advances obtained in recent years with new therapeutic agents, new approaches in surgical procedures and new diagnostic methods. The discovery of a plethora of cellular targets and the rational generation of selective targeting agents has opened an era of new opportunities and extraordinary challenges. The specificity of these agents renders them capable of specifically targeting the inherent abnormalities of cancer cells, potentially resulting in less toxicity than traditional nonselective cytotoxics. Among the many new types of rationally designed agents are therapeutics targeting various strategic facets of growth signal transduction, malignant angiogenesis, survival, metastasis and cell-cycle regulation. The evaluation of these agents is likely to require some changes from the traditional drug development paradigms to realize their full potential. Inhibition of the epidermal growth factor receptor and the vascular endothelial growth factor have provided proof of principle that disruption of signal cascades in patients with colorectal cancer has therapeutic potential. This experience has also taught us that resistance to such rationally developed targeted therapeutic strategies is common. In this article, we review the role of signal transduction in colorectal cancer, introduce promising molecular targets, and outline therapeutic approaches under development.
尽管近年来在新的治疗药物、手术方法和新的诊断方法方面取得了进展，但癌症患者的预后仍然很差。大量细胞靶点的发现和选择性靶向药物的合理生成开辟了一个新的机遇和巨大挑战的时代。这些药物的特异性使它们能够特异性地针对癌细胞固有的异常，潜在地导致比传统的非选择性细胞毒素毒性更小。在许多新的理性设计药物中，有针对生长信号转导、恶性血管生成、存活、转移和细胞周期调节的各种策略靶点的治疗方法。这些药物的评估可能需要从传统的药物开发模式进行一些改变，以充分发挥其潜力。表皮生长因子受体和血管内皮生长因子的抑制已经提供了一个原理证明，即破坏结直肠癌患者的信号级联具有治疗潜力。这一经验还告诉我们，对这种理性开发的靶向治疗策略的耐药性很常见。在本文中，我们综述了信号转导在结直肠癌中的作用，介绍了有前途的分子靶点，并概述了正在开发的治疗方法。
