Date of Award

January 2020

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Michael Girardi

Abstract

Cutaneous T cell lymphoma (CTCL) comprises of several heterogenous non-Hodgkin lymphomas where malignant cells are typically monoclonal CD4+ skin-homing T cells. Other than in rare exceptions, response rates to current FDA-approved therapies are only up to 50%. A hallmark of CTCL is exceptional genetic diversity of malignant cells, and due to the lack of classic driver mutations readily apparent in other lymphomas, drug development is not conducive to narrow single-target approaches. However, we believe that common synergistic pathways contribute to disease burden, and that these can be overcome through drug combinations. To this end, we designed and developed a protocol for in vitro High-Throughput Drug Screening (HTDS) that allows for conservation of limited patient samples while maximizing our potential to screen current and potential anti-CTCL agents, alone and in combination. Herein, we describe the implementation of the HTDS with candidate agent prioritization informed through bulk RNA-Seq data or library screening, and identify several agents (e.g. ruxolitinib, gentian violet) as promising clinical candidates.

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

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