Synergistic Relationship of Combinations Between Protons and Drugs on Neuroblastoma Cells to Induce Cell Death

Abstract

By Victoria Heyob, Biology

Advisor: John Perentesis

Presentation ID: AM_D11

Abstract: Apart from the combination of traditional cytotoxic chemotherapy with radiotherapy, little progress has been made in identifying optimal drug and radiotherapy combinations to improve the effectiveness or reduce the toxicity of cancer treatment. We seek to identify synergistic proton-drug combinations by screening a drug repositioning library of ~2,750 drugs, against a panel of well characterized, commercially available cell lines to discover novel treatment strategies for drug/radiotherapy combinations.Our hypothesis is that proton therapy can trigger cell death through a variety of mechanisms such as apoptosis, necrosis, autophagy, mitotic catastrophe, deregulation of cellular energetics/metabolism, senescence, and neo-antigen generation. Our goal is to identify novel synergistic relationships with combinatorial proton-drug treatment by exploiting proton induced mechanisms of cell death or targeting pathways of escape from proton treatment. Aim 1: To identify drug-proton combinations that are synergistic, antagonistic, and additive. Aim 2: To differentiate the mechanisms of action of photons and protons, and identify signatures unique to proton therapy within different histological and genomic landscapes.