Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel.
Oncologist. 2011;16 Suppl 1:23-9. doi: 10.1634/theoncologist.2011-S1-23.
The understanding of cellular signaling pathways in malignant tumors is an important aspect of cancer research and modern targeted therapy strategies. Growth factors and their receptors in particular are critical to modern cancer therapy research, because these factors control all phases of tumor development and metastasis. Most importantly, growth factors are responsible for cell survival under cytotoxic drugs and radiotherapy. These growth factor signaling pathways are composed of complex networks that have adapted to efficiently respond to certain disturbances, such as a single agent that targets one aspect of the pathway. Meanwhile, multiple insults to the pathway, such as combination therapy regimens, are known to be effective in shutting down these pathways and, consequently, killing the tumor cell. Research is currently under way to find new ways to exploit fragile aspects of oncogenic networks, such as uncommon, multiple perturbations that target essential hubs through immunotherapy, combinations of antibodies, heat shock protein inhibitors, or novel drug combinations. Complex growth factor signaling networks and novel methods to shut down these networks are described within a framework of engineering and mathematical concepts.
恶性肿瘤中细胞信号通路的理解是癌症研究和现代靶向治疗策略的一个重要方面。生长因子及其受体尤其对现代癌症治疗研究至关重要，因为这些因子控制着肿瘤发展和转移的所有阶段。最重要的是，生长因子负责在细胞毒性药物和放射治疗下的细胞存活。这些生长因子信号通路由复杂的网络组成，这些网络已经适应了有效地响应某些干扰，例如针对途径某一方面的单一药物。同时，已知对途径的多种损伤，如联合治疗方案，可有效关闭这些途径，并因此杀死肿瘤细胞。目前正在研究寻找利用致癌网络脆弱方面的新方法，例如通过免疫疗法、抗体组合、热休克蛋白抑制剂或新型药物组合针对关键枢纽的罕见、多重扰动。复杂的生长因子信号网络和关闭这些网络的新方法是在工程和数学概念的框架内描述的。
