A preclinical evaluation shows ONC201 reduces lung tumor incidence in KRASG12V mice, suggesting its potential as a preventive agent.
Key Points
This research aims to evaluate the efficacy of ONC201 in preventing lung cancer in a KRASG12V transgenic mouse model.
Generated male and female KRASG12V mice through in-house breeding.
Mice were randomized into placebo and treatment groups at six weeks of age.
Administered ONC201 at varying doses twice weekly from eight weeks to 36 weeks of age.
Euthanized mice at 36 weeks to assess tumor incidence and multiplicity.
Performed histopathology and immunoblotting to analyze tumor characteristics and signaling pathways.
Placebo group showed ∼100% lung tumor incidence with an average multiplicity of 12.2 in males and 11.7 in females.
ONC201 treatment reduced tumor multiplicity significantly in a dose-dependent manner, with reductions from 34% to 63% in males and 33% to 55% in females.
Histological analysis revealed a dose-dependent decrease in adenocarcinoma multiplicity with reductions from 53% to 86% (males) and 54% to 79% (females).
No clinical signs of toxicity were observed across all doses tested.
Cite This Study
Venkatachalam et al. (2026) studied this question.