Targeted therapy for mTORC1-driven tumours through HDAC inhibition by exploiting innate vulnerability of mTORC1 hyper-activation.

ABSTRACT:

Backgound

The mechanistic target of rapamycin complex 1 (mTORC1) is important in the development and progression of many cancers. Targeted cancer therapy using mTORC1 inhibitors is used for treatment of cancers; however, their clinical efficacies are still limited.

Methods

We recently created a new mouse model for human lymphangiosarcoma by deleting Tsc1 in endothelial cells and consequent hyper-activation of mTORC1. Using Tsc1^iΔEC tumour cells from this mouse model, we assessed the efficacies of histone deacetylase (HDAC) inhibitors as anti-tumour agents for mTORC1-driven tumours.

Results

Unlike the cytostatic effect of mTORC1 inhibitors, HDAC inhibitors induced Tsc1^iΔEC tumour cell death in vitro and their growth in vivo. Analysis of several HD

SUBMITTER: Yang F 

PROVIDER: S-EPMC7283252 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature