Therapeutic targeting of the p53 pathway in cancer stem cells.

Therapeutic targeting of the p53 pathway in cancer stem cells.
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DOI:
10.1517/14728222.2012.726985
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发表时间:
2012-12
影响因子:
5.8
通讯作者:
El-Deiry WS
El-Deiry WS
中科院分区:
医学2区
文献类型:
--
作者:
Prabhu VV;Allen JE;Hong B;Zhang S;Cheng H;El-Deiry WS

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癌症干细胞由于其在癌症进展、维持和治疗抗性中不可或缺的作用而成为癌症治疗的高调药物靶标。恢复野生型p53功能是一种有吸引力的新的治疗方法,用于治疗癌症,由于p53的强大的肿瘤抑制功能的充分描述。随着新出现的证据将p53和干细胞生物学密切联系起来,这种方法也提供了靶向癌症干细胞的机会。恢复野生型p53功能的治疗方法,与p53相关的癌症和正常干细胞生物学,以及p53对癌症干细胞的下游作用。通过直接靶向p53、其相互作用蛋白或其家族成员来恢复野生型p53功能有望成为一类新的癌症疗法。本文综述了这些疗法可能对正常和癌症干细胞的影响,基于目前的证据将p53信号与这些人群联系起来。
Cancer stem cells are a high profile drug target for cancer therapeutics due to their indispensable role in cancer progression, maintenance, and therapeutic resistance. Restoring wild-type 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 cancer stem cells. Therapeutic approaches to restore the function of wild-type p53, cancer and normal stem cell biology in relation to p53, and the downstream effects of p53 on cancer stem cells. The restoration of wild-type 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 cancer stem cells based on the current evidence linking p53 signaling with these populations.
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