靶向c-Myc的癌症治疗策略

Cancer Treatment Strategies by Targeting the Oncoprotein c-Myc

c-Myc是一种转录因子,参与Myc/Max/Mxd信号调控网络。c-Myc不仅调节机体的正常发育,在肿瘤的发生发展过程中也发挥着十分重要的作用。目前的研究显示,超过70%肿瘤中存在c-Myc突变或表达量的变化。因此,c-Myc靶向抑制剂可能成为肿瘤治疗的新策略。目前,临床上尚无针对c-Myc的治疗方法,但是随着靶向c-Myc临床应用研究的不断深入,以Omomyc为代表的抑制剂研究取得了较大的进展,并且c-Myc在肿瘤中的直接抑制可能发展为可行的临床治疗手段。虽然靶向c-Myc在癌症治疗中具有广阔的前景,但c-Myc的直接抑制目前仍存在诸多的风险与挑战。本综述中,首先,对c-Myc在细胞中的调节网络及其生物学功能进行简要的总结;其次,讨论靶向c-Myc及其同系物在肿瘤治疗中的潜在意义;另外,总结c-Myc作为一个潜在的临床治疗靶点应用于临床所面临的诸多挑战。最后,对目前已经发现的一些c-Myc抑制剂,例如小分子抑制剂以及蛋白质和肽类抑制剂的优缺点进行对比与探讨,并就其所存在的问题作出展望,从而为癌症中以c-Myc为靶点的临床治疗提供理论依据。

c-Myc is a transcription factor involved in the Myc/Max/Mxd signal regulatory network.c-Myc plays important roles in human development and the oncogenesis or progression of different types of tumors.Current studies have shown that c-Myc mutations or expression changes are present in more than 70%of tumors.Therefore,c-Myc-targeted inhibitors might become a new strategy for tumor therapy.Currently,there is no clinical treatment for targeting c-Myc.With the continuous study aiming at the c-Myc targeted clinical application,Omomyc has become a representative c-Myc inhibitor by direct inhibition of c-Myc in tumors,which may be a feasible clinical treatment strategy.Although targeting c-Myc has broad prospects in cancer treatment,direct inhibition of c-Myc still has many risks and challenges.Therefore,in this review,firstly,we will summarize the regulatory network and biological functions of c-Myc in cells.Secondly,the potential significance of targeting c-Myc or its homologues in tumor therapy will be discussed.Additionally,the challenges faced by c-Myc as a potential therapeutic target in clinical application will be summarized.Finally,we will also discuss the advantages and disadvantages of some c-Myc inhibitors that have been discovered to date,such as small molecule inhibitors and protein and peptide inhibitors,therefore providing the theoretical basis for c-Myc targeted clinical therapy in cancer.