Personalizing Lung Cancer Prevention Through a Reverse Migration Strategy

Abstract

Lung cancer is the deadliest cancer in the United States and worldwide. Tobacco use is the one of the primary causes of lung cancer and smoking cessation is an important step towards prevention, but patients who have quit smoking remain at risk for lung cancer. Finding pharmacologic agents to prevent lung cancer could potentially save many lives. Unfortunately, despite extensive research, there are no known effective chemoprevention agents for lung cancer. Clinical trials in the past, using agents without a clear target in an unselected population, have shown pharmacologic interventions to be ineffective or even harmful. We propose a new approach to drug development in the chemoprevention setting: reverse migration, that is, drawing on our experience in the treatment of advanced cancer to bring agents, biomarkers, and study designs into the prevention setting. By identifying molecular drivers of lung neoplasia and using matched targeted agents, we hope to personalize therapy to each individual to develop more effective, tolerable chemo-prevention. Also, advances in risk modeling, using not only clinical characteristics but also biomarkers, may help us to select patients better for chemoprevention efforts, thus sparing patients at low risk for cancer the potential toxicities of treatment. Our institution has experience with biomarker-driven clinical trials, as in the recently reported Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial, and we now propose to bring this trial design into the prevention setting.

Precision Medicine Clinical Trials: Defining New Treatment Strategies

“…BATTLE-Prevention will use information from advanced cancer treatment to bring agents and biomarkers into the adjuvant setting to treat patients with stage I-IIIA NSCLC to prevent recurrence. 19,20 …”

Headway and Hurdles in the Clinical Development of Dietary Phytochemicals for Cancer Therapy and Prevention: Lessons Learned from Vitamin A Derivatives

“…Bexarotene plus erlotnib had significant activity in patients whose tumors overexpressed cyclin D1 as compared to those cases on erlotnib therapy alone (99). An interesting prospective BATTLE prevention trial is currently being planned where patients with resectable NSCLC will be randomized to chemoprevention protocols based on their marker profile (100). Those with overexpression of cyclin D1 will receive erlotnib and bexarotene and the endpoint will be cancer recurrence.…”