NQO1-dependent, Tumor-selective Radiosensitization of Non-small Cell Lung Cancers.

ABSTRACT:

Purpose

Development of tumor-specific therapies for the treatment of recalcitrant non-small cell lung cancers (NSCLC) is urgently needed. Here, we investigated the ability of β-lapachone (β-lap, ARQ761 in clinical form) to selectively potentiate the effects of ionizing radiation (IR, 1-3 Gy) in NSCLCs that overexpress NAD(P)H:Quinone Oxidoreductase 1 (NQO1).

Experimental design

The mechanism of lethality of low-dose IR in combination with sublethal doses of β-lap was evaluated in NSCLC lines in vitro and validated in subcutaneous and orthotopic xenograft models in vivo. Pharmacokinetics and pharmacodynamics (PK/PD) studies comparing single versus cotreatments were performed to validate therapeutic efficacy and mechanism of action.

Results

β-Lap administr

SUBMITTER: Motea EA 

PROVIDER: S-EPMC6788754 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature