Laboratory of Molecular Pharmacology, Dept of Oncology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Curr Med Chem. 2010;17(36):4433-47. doi: 10.2174/092986710794182999.
Phisiological activation of PI3K pathway is necessary for cells to regulate many different physiological processes such as transcription, protein synthesis, metabolic responses and membrane trafficking. Abnormal activation of the PI3K pathway leads to an increased activity resulting in tumor onset, maintenance, progression and invasion. Both genetic and epigenetic alterations could affect the normal pathway's activation. Ovarian cancer is the leading cause of death from gynaecological malignancies in the western world. PI3K pathway has been recorded as one of the most deregulated signalling pathway in many tumors, including ovarian ones. So it could be considered an attractive target to be investigated with the various classes of chemical compounds already present or in development. In this rewiew we'll try to discuss the published data of the inhibitors targeting members of the PI3K/ akt/ mTOR pathway in the ovarian cancer setting from a preclinical and clinical point of view, with particular emphasis on drugs combination and strategies of administration. Relevant issues and limitations to the use of particular compounds will be also addressed.
PI3K 通路的生理激活对于细胞调节许多不同的生理过程是必要的，如转录、蛋白质合成、代谢反应和膜运输。PI3K 通路的异常激活导致活性增加，从而导致肿瘤的发生、维持、进展和侵袭。遗传和表观遗传的改变都可能影响正常通路的激活。在西方世界，卵巢癌是妇科恶性肿瘤导致死亡的主要原因。PI3K 通路已被记录为许多肿瘤中最失调的信号通路之一，包括卵巢癌。因此，它可以被认为是一个有吸引力的靶点，可以用现有的或正在开发的各种化学化合物进行研究。在这篇综述中，我们将从临床前和临床的角度，尝试讨论针对卵巢癌中 PI3K/akt/mTOR 通路成员的抑制剂的已发表数据，特别强调药物联合和给药策略。还将讨论使用特定化合物的相关问题和限制。
