Queen Mary University of London, Barts and The London School of Medicine and Dentistry, Blizard Institute of Cell and Molecular Science, Centre for Diabetes, Inositide Signalling Group, London E1 2AT, UK.
Curr Pharm Des. 2010;16(12):1410-6. doi: 10.2174/138161210791033950.
The resistance of many types of cancer to chemotherapies represents the major hurdle in successful cancer treatment. Cancer cells can escape the toxic effect of most commonly used drugs despite their different chemical structure and intracellular targets. The mechanisms underlying the failure of chemotherapeutic drugs have been well studied. Here I review the role of a signalling pathway activated by the lipid kinase phosphoinositide 3-kinase (PI3K) and the serine/threonine kinase, protein kinase B (PKB) or Akt, in chemotherapeutic resistance. Activation of this pathway plays a key role in different cellular functions such as growth, migration survival and differentiation. Data accumulated in the last decade have established that this pathway plays a key role in cancer development and progression. More recently it has been shown that this pathway plays also a key role in resistance to chemotherapy. Therefore drugs designed to specifically target this pathway are under development to be used as single agent and in combination to chemotherapy to overcome therapeutic resistance.
许多类型的癌症对化疗的耐药性是癌症治疗成功的主要障碍。尽管这些药物具有不同的化学结构和细胞内靶点，但癌细胞可以逃避大多数常用药物的毒性作用。化疗药物失效的机制已经得到了很好的研究。在这里，我回顾了由脂质激酶磷脂酰肌醇 3-激酶 (PI3K) 和丝氨酸/苏氨酸激酶蛋白激酶 B (PKB) 或 Akt 激活的信号通路在化疗耐药性中的作用。该途径的激活在不同的细胞功能中起着关键作用，如生长、迁移、存活和分化。过去十年积累的数据表明，该途径在癌症的发生和发展中起着关键作用。最近的研究表明，该途径在化疗耐药性中也起着关键作用。因此，正在开发专门针对该途径的药物，作为单一药物或与化疗联合使用，以克服治疗耐药性。
