Centre for Cell Signalling, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Biochem J. 2013 Jun 15;452(3):e11-3. doi: 10.1042/BJ20130617.
The success of targeted therapies in treating cancer over the last decade has been tempered by acquired drug resistance that follows long-term treatment. There is also emerging evidence for innate mechanisms of cancer cell resistance to targeted therapy that pre-exist as parallel signalling pathways. This aspect is explored by the Alessi group and collaborators from AstraZeneca in this issue of the Biochemical Journal, who identify a subset of breast cancer cell lines that are intrinsically resistant to Akt inhibition through constitutive up-regulation of the related AGC serine/threonine kinase SGK1 (serum- and glucocorticoid-regulated kinase 1). The study could help to profile tumours for sensitivity to Akt inhibitors and once more highlights the therapeutic complexity of cancer and the importance of exploring combination therapies in the clinic.
过去十年中，靶向治疗在癌症治疗方面取得了成功，但长期治疗后会出现获得性耐药性。也有越来越多的证据表明，癌细胞对靶向治疗存在固有耐药机制，这些机制以前是平行的信号通路。Alessi 小组和阿斯利康的合作者在本期《生物化学杂志》上探讨了这一方面，他们鉴定出一组乳腺癌细胞系通过组成性上调相关的 AGC 丝氨酸/苏氨酸激酶 SGK1（血清和糖皮质激素调节激酶 1）对 Akt 抑制具有内在耐药性。这项研究有助于为对 Akt 抑制剂敏感的肿瘤进行分类，并再次强调了癌症治疗的复杂性和探索联合治疗在临床上的重要性。
