Accession Number:

AD1113585

Title:

A Novel Agent for Lung Cancer Prevention

Descriptive Note:

[Technical Report, Annual Report]

Corporate Author:

The Pennsylvania State University

Personal Author(s):

Report Date:

2020-07-01

Pagination or Media Count:

15

Abstract:

Lung cancer is the leading cause of cancer related deaths in the United States. Despite the identification of several preventive agents and strategies, optimal prevention of lung cancer, especially in smokers and ex-smokers who are at high risk, has not been achieved. More effective agents are therefore required that would safely achieve prevention without drastic side effects. Novel compounds which are rational modifications of well-established chemopreventive agents and follow a similar mechanism of action, but with enhanced potency, reduced toxicity, and lower dose requirement, may be clinically more relevant. We have developed one such agent p-XS-Asp, designed by conjugating two well known chemopreventive agents i.e. 1,4-phenylenebismethylene-selenocyanate p-XSC and aspirin, which has shown promising lung cancer preventive properties in our preliminary in vitro and animal studies. The long-term goal of this project is to develop this rationally-designed, effective, and safe agent for the prevention and interception of smoking-related lung cancer. Given the preeminence of tobacco carcinogens in initiating and driving lung cancer, we hypothesize that p-XS-Asp exerts chemopreventive effect at both initiation and post-initiation stages of lung tumorigenesis through i inhibition of Phase I carcinogen activation, ii induction of Phase II carcinogen detoxification, iii suppressing activation of AKTCOX-2 pathways, and iv inhibiting proliferation and viability of preneoplastic cells. The specific objectives of this proposal are to i test the efficacy of p-XS-Asp for inhibiting lung cancer development at different stages of NNK-induced carcinogenesis using the AJ mouse lung cancer model, ii evaluate the pharmacological and biochemical mechanisms by conducting p-XS-Asp metabolism and comparing PKbioavailability with p-XSC, and iii elucidate mechanisms of actions of anti-initiation and anti-progression effects of p-XS-Asp.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

[A, Approved For Public Release]