A04 Dissecting aberrant functions of the ubiquitin proteasome system in the treatment-induced evolution of Mantle Cell Lymphoma
Mantle Cell Lymphoma (MCL) is an aggressive and incurable B-cell malignancy. Major treatment modalities include DNA damaging agents, proteasome inhibitors, B-cell receptor inhibitory agents and immunomodulatory drugs (IMiDs) whose anti-tumor activities and induced resistance mechanisms involve the ubiquitin proteasome system (UPS).
This project aims to dissect aberrant components of the UPS that contribute to treatment-induced evolution of MCL and unravel their role as targets and biomarkers.
Figure Legend: The Ubiquitin Proteasome System (UPS) regulates key aspects of cellular life including growth, proliferation, survival, genome maintenance and differentiation. As such, the UPS is directly or indirectly involved in mediating the activity of various anti-neoplastic treatment modalities. At the same time, the UPS is an important target of tumor specific alterations that enable resistance mechanisms. Using an interdisciplinary approach that comprises tumor genomics, functional proteomics and cell biology, our project aims to functionally dissect such aberrations in MCL to generate a framework that will help to understand treatment-induced evolution in MCL.