Therapeutic potential of combating cancer by restoring wild-type p53 through mRNA nanodelivery

IF 4.2 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Nanomedicine : nanotechnology, biology, and medicine Pub Date : 2024-01-08 DOI:10.1016/j.nano.2024.102732

Divya Kamath PhD , Tomoo Iwakuma MD PhD , Stefan H. Bossmann PhD

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Abstract

Among the tumor suppressor genes, TP53 is the most frequently mutated in human cancers, and most mutations are missense mutations causing production of mutant p53 (mutp53) proteins. TP53 mutations not only results in loss of function (LOH) as a transcription factor and a tumor suppressor, but also gain wild-type p53 (WTp53)-independent oncogenic functions that enhance cancer metastasis and progression (Yamamoto and Iwakuma, 2018; Zhang et al., 2022). TP53 has extensively been studied as a therapeutic target as well as for drug development and therapies, however with limited success. Achieving targeted therapies for restoration of WTp53 function and depletion or repair of mutant p53 (mutp53) will have far reaching implication in cancer treatment and therapies. This review briefly discusses the role of p53 mutation in cancer and the therapeutic potential of restoring WTp53 through the advances in mRNA nanomedicine.

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通过 mRNA 纳米输送恢复野生型 p53 抗癌的治疗潜力

在肿瘤抑制基因中，TP53是人类癌症中最常发生突变的基因，大多数突变都是错义突变，导致产生突变p53（mutp53）蛋白。TP53突变不仅会导致作为转录因子和肿瘤抑制因子的功能缺失（LOH），还会获得野生型p53（WTp53）依赖的致癌功能，从而增强癌症的转移和进展（Yamamoto and Iwakuma, 2018; Zhang et al.）人们已将 TP53 作为治疗靶点以及药物开发和疗法进行了广泛研究，但成效有限。实现恢复 WTp53 功能和消耗或修复突变 p53（mutp53）的靶向疗法将对癌症治疗和疗法产生深远影响。本综述简要讨论了 p53 突变在癌症中的作用，以及通过 mRNA 纳米药物的进步恢复 WTp53 的治疗潜力。

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来源期刊

Nanomedicine : nanotechnology, biology, and medicine 工程技术-纳米科技

CiteScore

11.10

自引率

0.00%

发文量

133

审稿时长

42 days

期刊介绍： The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine. Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.