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TNBC is an aggressive and metastatic subtype of breast cancer in which the TP53 mutation occurs frequently and is associated with particularly poor outcomes. Mutations in TP53 can disrupt the intrinsic function of the tumor suppressor as well as acquire oncogenic gain-of-function (GOF) activities. However, little is known about its oncogenic GOF mediators and functions. Targeted therapy for TNBC patients is thus one of the most urgent needs in breast cancer therapeutics, and identifying genes that have synthetic lethal interactions with mutant TP53 may be a promising approach. Sequential analysis of RNA-seq followed by high-throughput RNA interference screening (HTS-RNAi screening), as an intrinsic cellular mechanism for the identification of genes with synthetic lethality of mutant TP53, is a promising strategy for the treatment of mutant TP53 in TNBC and determining its impact on tumorigenesis.

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High-Throughput RNA Interference Screen Targeting Synthetic-Lethal Gain-of-Function of Oncogenic Mutant TP53 in Triple-Negative Breast Cancer

  • 实验方案

  • 发表日期：

    2026年

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  • Susumu Rokudai

摘要

TNBC is an aggressive and metastatic subtype of breast cancer in which the TP53 mutation occurs frequently and is associated with particularly poor outcomes. Mutations in TP53 can disrupt the intrinsic function of the tumor suppressor as well as acquire oncogenic gain-of-function (GOF) activities. However, little is known about its oncogenic GOF mediators and functions. Targeted therapy for TNBC patients is thus one of the most urgent needs in breast cancer therapeutics, and identifying genes that have synthetic lethal interactions with mutant TP53 may be a promising approach. Sequential analysis of RNA-seq followed by high-throughput RNA interference screening (HTS-RNAi screening), as an intrinsic cellular mechanism for the identification of genes with synthetic lethality of mutant TP53, is a promising strategy for the treatment of mutant TP53 in TNBC and determining its impact on tumorigenesis.