Hammaker D, Sweeney S, Firestein G S
Division of Rheumatology, Allergy and Immunology, UCSD School of Medicine, La Jolla, CA 92093, USA.
Ann Rheum Dis. 2003 Nov;62 Suppl 2(Suppl 2):ii86-9. doi: 10.1136/ard.62.suppl_2.ii86.
Signal transduction pathways regulate cellular responses to stress and play a critical role in inflammation. The complexity and specificity of signalling mechanisms represent major hurdles for developing effective, safe therapeutic interventions that target specific molecules. One approach is to dissect the pathways methodically to determine their hierarchy in various cell types and diseases. This approach contributed to the identification and prioritisation of specific kinases that regulate NF-kappa B and the mitogen activated protein (MAP) kinase cascade as especially attractive targets. Although significant issues remain with regard to the discovery of truly selective kinase inhibitors, the risks that accompany inhibition of fundamental signal transduction mechanisms can potentially be decreased by careful dissection of the pathways and rational target selection.
信号转导通路调节细胞对应激的反应，并在炎症中发挥关键作用。信号机制的复杂性和特异性是开发针对特定分子的有效、安全治疗干预措施的主要障碍。一种方法是系统地剖析这些通路，以确定它们在各种细胞类型和疾病中的层级关系。这种方法有助于识别和优先考虑特定的激酶，这些激酶调节核因子κB和丝裂原活化蛋白（MAP）激酶级联反应，是特别有吸引力的靶点。尽管在发现真正具有选择性的激酶抑制剂方面仍然存在重大问题，但通过仔细剖析信号通路和合理选择靶点，抑制基本信号转导机制所带来的风险可能会降低。
