Clinical Experimental Oncology Laboratory, National Cancer Institute Giovanni Paolo II, Viale O. Flacco, 65, 70124 Bari, Italy.
Curr Pharm Des. 2013;19(5):918-26.
Single-agent therapy with molecularly targeted agents has shown limited success in tumor growth control, mainly because escape or resistance mechanisms are activated once a signalling molecule is inhibited. Rational combinations of target-specific agents could counteract this response providing a useful strategy in cancer treatment. In this regard, the EGFR and mTOR inhibitors have been used together to generate a synergistic effect and maximize the efficacy of each individual agent. Overall, the in vivo and in vitro evidences support the utilization of combinations targeting EGFR and mTOR, for malignancies characterized by deregulated EGFR/PI3K/Akt/ mTOR signalling cascade; whereas the clinical experience points out that the assessment of the therapeutic value of such combination awaits further investigations.
单药分子靶向治疗在肿瘤生长控制方面的疗效有限，这主要是因为一旦信号分子被抑制，逃逸或耐药机制就会被激活。针对特定靶点的药物联合应用可以对抗这种反应，为癌症治疗提供一种有效的策略。在这方面，EGFR 和 mTOR 抑制剂已被联合应用以产生协同作用，最大限度地提高每个药物的疗效。总的来说，体内和体外的证据支持针对 EGFR 和 mTOR 的联合治疗，用于具有失调的 EGFR/PI3K/Akt/mTOR 信号级联的恶性肿瘤；而临床经验表明，这种联合治疗的治疗价值评估还需要进一步的研究。
