Biomarkers for Predicting Response to Immune Checkpoint Blockers
Abstract
Background and Objectives: Cancer remains a leading cause of mortality among Americans, and the lung is the primary site of origin for these deaths. Among available treatments for metastatic lung cancer, immune checkpoint blockers are associated with the best survival rates, with anti-PD1/PDL1 monoclonal antibodies (mAb) considered to be the industry standard for treatment. Yet, even this therapeutic advance benefits only a minority (<20%) of metastatic lung cancer patients. Furthermore, there are no good markers for sorting which patients will or will not respond to treatment. Our objective is to identify biomarkers that reliably prognosticate responsiveness (vs. resistance) of metastatic lung cancer patients to anti-PD1/PDL1 mAb. Lung Cancer Program Areas of Emphasis: Our proposal will (1) improve management of lung cancer patients; (2) understand how lung cancer rapidly grows; (3) identify biologic markers that distinguish which patients will benefit or not benefit from anti-PD1/PDL1 therapy; and (4) understand how patients acquire resistance to this treatment. Ultimate Applicability of the Research: What types of patients will it help, and how will it help them? Our studies will identify biomarkers that predict which patients with metastatic lung cancer will respond (vs. not respond) to anti-PD1/PDL1 mAb. What are the potential clinical applications, benefits, and risks? Identifying reliable biomarkers will save time, money, and morbidity associated with anti-PD1/PDL1 therapy. What is the projected time it may take to achieve a clinically relevant outcome? Our studies will require 3 years of research. What are the likely contributions of this study to advancing the field of lung cancer research? Identifying reliable prognostic markers will directly benefit treatment of patients with lung cancer. Our studies will also improve our understanding of T-cell immunity in lung cancer biology, particularly the mechanisms involved in interactions between the PD1/PDL1 pathway and our newly discovered DC-HIL/syndecan-4 pathway. The new knowledge gained will yield insight into whether blocking both pathways yields additive, synergistic, null, or counteractive effects, and thus a basis for further studies. How is the project relevant to military Service members, Veterans, and their families? Lung cancer is the leading cause of metastasis in the United States and a common cause of morbidity and mortality among military Service members, Veterans, and their families. Our outcomes should improve the survival rates of afflicted patients and lead to savings in medical expenses.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810312
Entities
People
- Kiyoshi Ariizumni
Organizations
- United States Army
- University of Texas Southwestern Medical Center