Ziegler David S, Kung Andrew L
Department of Pediatric Oncology, Dana-Farber Cancer Institute and Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Curr Opin Oncol. 2008 Jan;20(1):97-103. doi: 10.1097/CCO.0b013e3282f310f6.
Anti-apoptotic mechanisms contribute to the development of cancer and the resistance of cancer cells to antitumor therapies. This review focuses on the progress towards clinical application of therapies that directly modulate the apoptosis pathways.
A growing understanding of the mechanisms that control apoptosis has generated a number of strategies for modulating apoptotic pathways, including activation of death receptors and neutralization of anti-apoptotic proteins. Striking antitumor efficacy has been achieved in preclinical cancer models. To date, early-phase testing has not yet established the clinical utility of these strategies.
There is every reason to be optimistic that the wealth of knowledge about the molecular controls of apoptosis will eventually be translated into new clinical therapies for cancer. It is likely that the optimum utility of these pro-apoptotic therapies will be in combination with other treatment modalities, and careful patient selection will be necessary.
抗凋亡机制在癌症发展以及癌细胞对抗肿瘤治疗的耐药性方面发挥作用。本综述着重探讨直接调节凋亡途径的疗法在临床应用方面的进展。
对控制凋亡机制的深入了解催生了多种调节凋亡途径的策略，包括激活死亡受体和中和抗凋亡蛋白。在临床前癌症模型中已取得显著的抗肿瘤疗效。迄今为止，早期试验尚未确立这些策略的临床实用性。
有充分理由乐观地认为，关于凋亡分子调控的丰富知识最终将转化为新的癌症临床治疗方法。这些促凋亡疗法的最佳效用可能在于与其他治疗方式联合使用，并且需要仔细挑选患者。
