Author ORCID Identifier
Date Available
2-12-2018
Year of Publication
2018
Degree Name
Doctor of Philosophy (PhD)
Document Type
Doctoral Dissertation
College
Pharmacy
Department/School/Program
Pharmaceutical Sciences
First Advisor
Dr. Esther P. Black
Second Advisor
Dr. Jeffery Talbert
Abstract
Precision medicine has allowed for the development of monoclonal antibodies that unmask the anti-tumor immune response. These agents have provided some patients durable clinical benefit. However, PD-1 and PD-L1 inhibitor therapies are effective in a small group (10-20%) of non-small cell lung cancer (NSCLC) patients when used as single-agent therapy. The approved companion diagnostic is expression of the immune cell surface molecule, programmed death ligand 1 (PD-L1), on tumors measured by immunohistochemistry (IHC). Studies in tumor biology and immune surveillance dictate that PD-1 inhibitor efficacy should depend on the level of PD-L1 expression; however, the literature has not followed with convincing evidence. The limitations of this test include timing of tissue acquisition, tumor heterogeneity, and timing of therapy relative to the expression of PD-L1. In addition, the requirement of analyzing tumor tissue biopsy samples from a patient is cumbersome. Thus, a peripheral blood biomarker that predicts efficacy of PD-1/PD-L1 inhibition would be optimal for precise and cost-effective treatment. A history of chronic inflammatory diseases may be advantageous for a cancer patient who is treated with PD-1/PD-L1 inhibitors and may allow them to then mobilize a swift immune response to tumor cells. Specific biological components of this persistent inflammation may predict PD-1 inhibitor response. We have taken a novel approach to leverage national healthcare claims data that couples patient history with response to therapy. We have identified potential peripheral blood biomarkers of response to PD-1/PD-L1 inhibitors using a combination of healthcare outcomes and molecular markers that correlate with therapeutic efficacy.
Digital Object Identifier (DOI)
https://doi.org/10.13023/ETD.2018.045
Recommended Citation
El-Refai, Sherif M., "EXPLORING THE EFFECT OF CHRONIC INFLAMMATION ON RESPONSE TO IMMUNE CHECKPOINT INHIBITORS IN CANCER" (2018). Theses and Dissertations--Pharmacy. 82.
https://uknowledge.uky.edu/pharmacy_etds/82
