Baer-Dubowska Wanda
University of Medical Sciences in Poznań, Department of Pharmaceutical Biochemistry Grunwaldzka 6, 60-780 Poznań.
Acta Pol Pharm. 2006 Sep-Oct;63(5):369-73.
After a quarter of a century of rapid advances in cancer research, the focus of oncological drug development has shifted from cytotoxic chemotherapy to rationally designed agents that target specific molecules associated with malignant cells or their environment. Carcinogenic process is driven by mutation, but there are many epigenetic variables which could be the targets of early intervention before invasion and metastasis occur. Chemoprevention is the inhibition, retardation or reversal of carcinogenic processes by pharmacological or natural agents targeting these pathways in high-risk individuals. This approach was developed more than 30 years ago and its credibility was enhanced by the positive results of clinical trials involving subjects with risk of developing breast cancer and colon tumors. So far however, not many clinical trials provided satisfying results, not only because of the lack of efficacy or side toxic effects of chemopreventive agents, but also the lack of precise biomarkers monitoring their effects. In spite of all these obstacles, the field of cancer chemoprevention is very active, not only because of its accelerating scientific base, but also because is vitally needed. New information from molecular studies has identified specific molecular targets for chemopreventive agents. These include regulatory molecules such as Nrf2, epidermal growth factor receptor kinases, components of the Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway, nuclear factor-kappaB, and cyclin D. The development of new drugs for the control of these targets that are both safe and effective will be important for the future of cancer chemoprevention.
在癌症研究历经四分之一个世纪的快速发展之后，肿瘤药物研发的重点已从细胞毒性化疗转向了合理设计的药物，这些药物靶向与恶性细胞或其环境相关的特定分子。致癌过程由突变驱动，但存在许多表观遗传变量，它们可能是侵袭和转移发生之前早期干预的靶点。化学预防是指通过针对高危个体中这些途径的药理或天然药物来抑制、延缓或逆转致癌过程。这种方法在30多年前就已出现，并且涉及有患乳腺癌和结肠肿瘤风险受试者的临床试验的积极结果增强了其可信度。然而，到目前为止，没有多少临床试验能提供令人满意的结果，这不仅是因为化学预防药物缺乏疗效或存在副作用，还因为缺乏监测其效果的精确生物标志物。尽管存在所有这些障碍，癌症化学预防领域仍然非常活跃，这不仅是因为其科学基础不断加速，还因为它至关重要。分子研究的新信息已经确定了化学预防药物的特定分子靶点。这些靶点包括诸如Nrf2、表皮生长因子受体激酶、Janus激酶 - 信号转导和转录激活因子（JAK - STAT）途径的组成部分、核因子 - κB以及细胞周期蛋白D等调节分子。开发既能控制这些靶点又安全有效的新药对于癌症化学预防的未来至关重要。
