Investigating wild type ALK as a dependency in neuroblastoma
Mentor Name: Yael Mossé
Neuroblastoma is an incredibly diverse and dangerously progressive pediatric cancer that emerges in the developing sympathetic nervous system; the average age of diagnosis is 17 months old. Previous research has focused on anaplastic lymphoma kinase (ALK), a gene that encodes a receptor tyrosine kinase protein whose family is involved in cell growth. In neuroblastoma, mutated ALK is constitutively active, which causes uncontrolled cell division that contributes to neuroblastoma's growth. This project aims to investigate the role of wild-type ALK protein in neuroblastoma. In addition to ALK mutations and amplifications, many neuroblastoma tumors express native ALK on the cell surface. We propose a project to investigate the potential dependency of neuroblastoma cells on ALK in the presence and absence of its ligand. We hypothesize that wild-type ALK is a neuroblastoma dependency in the absence of an underlying genetic alteration. We postulate that, in the presence of ligand, ALK signaling will be provoked and may render these cells susceptible to ALK inhibition with either small molecules like lorlatinib or with antibody-based approaches.
