Tyrosine kinases, a ubiquitous and diverse family of enzymes, are of considerable clinical interest because they directly contribute to the development of cancer. A growing number of tyrosine kinase inhibitors are in clinical use with many more in development.

 

Bruton's tyrosine kinase (BTK) is a receptor-type tyrosine kinase critical for B cell maturation. It is encoded by the BTK gene, located on the X chromosome. Mutations in BTK cause a primary immunodeficiency phenotype linked to the failure of pre-B cells to mature (a disease termed Bruton's agammaglobulinemia). Due to its control of B cell proliferation and survival, aberrant activity of BTK leads to B cell tumorigenicity. Several BTK inhibitors are used for the clinical treatment of various forms of lymphoma, including chronic lymphocytic leukemia (CLL). Covalent BTK inhibitors (BTKis) have led to an unprecedented improvement in CLL outcomes. However, disease progression on covalent BTKis, driven by histologic transformation or selective expansion of BTK-mutated CLL clones, remains a major challenge.

 

Dr. Aishath's talk will focus on:

- Targeting BTK in CLL

- Comparative analysis of covalent and non-covalent BTK inhibitors

- Resistance mechanisms to BTK inhibitors

 

Dr. Baron will speak about:

- Tools to study kinases

- CRISPR/Cas9 Human Kinase Knockout Lentivirus Library

- Unique assays to study JAK inhibitors

- Off-the-shelf cell-based reporter systems