Modulating Nup37 For Novel Cancer Therapies

Novel Therapeutics & Platforms

Maximiliano D'Angelo, PhD (Sanford Burnham Prebys)

Hatim Husain, MD (UC San Diego)

Susanne Heyen-Genel, PhD (Sanford Burnham Prebys)

Lung cancer is a leading cause of death worldwide, highlighting the need for new therapies. Nuclear pore complexes (NPCs), the channels connecting the nucleus to the cytoplasm, are built from 32 different proteins or nucleoporins. Emerging evidence shows that cells modify NPCs and nucleoporins to regulate specific functions, and cancer cells exploit this plasticity to promote tumorigenesis, making them dependent on these alterations and rendering certain nucleoporins key vulnerabilities. We found that the nucleoporin Nup37 is a critical dependency of lung cancer cells that can be leveraged for targeted therapies. We established and validated a novel high-throughput assay to screen for Nup37 modulators. Our goal is to perform a large-scale screen to identify small molecules that reduce Nup37 levels and validate lead compounds for anti-lung cancer efficacy. We expect to identify the first Nup37 inhibitors and lay the foundation for the development of selective lung cancer therapies.