Targeting Alternative N-terminal Kinases
Potential of treating epithelial tumors with therapeutics based on BTK-C, a palmitoylated isoform of Bruton’s tyrosine kinase (BTK)
Background
Bruton’s tyrosine kinase (BTK) plays an active role in the development, maturation, and signaling of B cells. BTK regulates cell proliferation, survival, and migration in various B-cell malignancies, such as Burkitt lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and others. Several therapeutics that target BTK have been approved by the Food and Drug Administration for the treatment of several hematological malignancies. Development of BTK-based therapies has transformed the treatment of several B-cell malignancies. One isoform of BTK, BTK-C, is uniquely expressed in a wide variety of epithelial tumor types where it impacts apoptosis resistance, therapeutic escape, and glucose uptake.
Technology Overview
This University at Albany technology is based on the fact that BTK-C differs from other BTK isoforms in that it is expressed in solid tumors, has a unique mRNA, and is palmitoylated (undergoes covalent attachment of fatty acids) on two cysteine residues. Palmitoylation affects localization and regulation of BTK-C in epithelial tumor cells where it functions as an important survival factor. Nine other soluble kinases possess similar alternative N-termini (ANT) encoding palmitoylated isoforms. Tumors that do not express BTK-C have higher levels of ERBB2, the estrogen receptor, and the androgen receptor among others. This may mean that targeting BTK-C with inhibitors could be used in tumors that do not respond to inhibitors of other proteins.
Stage of Development
Technology Readiness Level (TRL): 3 - Experimental proof of concept.
Benefits
- Can treat tumors that do not respond to inhibitors of other proteins.
- May be applicable to a number of different tumor types.
Opportunity
This technology is available for licensing and would be of interest to anyone involved in the development of cancer therapeutics, including:
- Pharmaceutical companies.
- Hospitals.
- Medical research laboratories.
- Universities and other educational facilities.