Penn State Hershey Cancer Institute, Penn State College of Medicine, Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Department of Medicine (Hematology/Oncology), 500 University Drive, Room T4423, Hershey, PA 17033, USA.
Expert Opin Ther Targets. 2012 Dec;16(12):1161-74. doi: 10.1517/14728222.2012.726985. Epub 2012 Sep 24.
Cancer stem cells (CSCs) are a high profile drug target for cancer therapeutics due to their indispensable role in cancer progression, maintenance and therapeutic resistance. Restoring wild-type (WT) p53 function is an attractive new therapeutic approach for the treatment of cancer due to the well-described powerful tumor suppressor function of p53. As emerging evidence intimately links p53 and stem cell biology, this approach also provides an opportunity to target CSCs.
This review covers the therapeutic approaches to restore the function of WT p53, cancer and normal stem cell biology in relation to p53 and the downstream effects of p53 on CSCs.
The restoration of WT p53 function by targeting p53 directly, its interacting proteins or its family members holds promise as a new class of cancer therapies. This review examines the impact that such therapies may have on normal and CSCs based on the current evidence linking p53 signaling with these populations.
癌症干细胞（CSCs）是癌症治疗药物的一个备受关注的靶点，因为它们在癌症进展、维持和治疗抵抗中起着不可或缺的作用。由于 p53 的强大肿瘤抑制功能已有充分描述，恢复野生型（WT）p53 的功能是一种有吸引力的新治疗方法。由于新兴证据将 p53 与干细胞生物学紧密联系起来，这种方法也为靶向 CSCs 提供了机会。
本综述涵盖了恢复 WT p53 功能的治疗方法，涉及与 p53 相关的癌症和正常干细胞生物学以及 p53 对 CSCs 的下游影响。
通过直接靶向 p53、其相互作用蛋白或其家族成员来恢复 WT p53 的功能，有望成为一类新的癌症治疗方法。本综述根据目前将 p53 信号与这些群体联系起来的证据，检查了此类治疗方法可能对正常和 CSCs 产生的影响。
