Diagnostic and therapeutic biomarkers in human cancers

Description:

Project ID D2020-01

 

Background

IQGAP is a regulatory scaffold protein that organizes actin and microtubule cytoskeleton to regulate cell movement, division, and adhesion. It is an oncoprotein that can transduce signals emanating from surface receptors to the nucleus to control gene expression. IQGAP1 protein is regulated by addition or removal of phosphate groups, which changes the form of the protein and allow it to interact and scaffold with a number of different proteins as well as change localizations within the cell. For normal cell function, IQGAP1 must cycle between the two phosphorylation-forms.  If locked in one form, it can cause different types of disease, including cancer. Although IQGAP1 has been proposed as a clinical target, its unique pathway and mechanism are not well understood.

Invention Description

Researchers from the University of Toledo have developed a diagnostic kit for analysis of solid tumors. In addition to quantifying expression levels of both IQGAP1 and additional downstream markers, IQGAP1 is analyzed for mislocalization and aberrant phosphorylation. Patients falling outside of the normal range are diagnosed with cancer and treated with the appropriate therapy. Treatment options from this diagnostic could include a drug that localizes IQGAP1 in the centrosomes, one that reduces phosphorylation of IQGAP1 or corrects an over- or under-expression of a downstream marker. The invention identifies a new IQGAP1-pathways leading to centrosome aberrations known to be associated with cancer and provides tools for diagnosis and treatment. In this pathway, the kinase Mnk1 and the transcription factor NRF1 were identified as personalized diagnostic biomarkers and therapeutic targets in triple negative breast cancer (TNBC) and lung cancer

 

Applications

-       Diagnostic for solid tumors

-       Adds confidence in prescribing IQGAP1-IR-WW peptide, inhibitors against phospho-IQGAP1, specific stress related kinases (such as JNK and Mnk1), antagonists or agonists for ADR (sigma receptor), antimicrotubule drugs such as paclitaxel (Taxol), vinorelbine (Navelbine), docetaxel (Taxotere), and vinblastine (Valban)

 

Advantages

•       Capable of identifying patients best suited for treatments targeting the IQGAP1-related pathways e.g. in centrosome biology, cellular stress or Wnt signaling pathway

•       Takes into account more than just expression levels of IQGAP1

•       Enables personalized medicine for cancer

•       Treatment of triple negative breast cancer or lung cancer, generally applies to organ-nonspecific tumors

 

IP Status:       Patent Pending

 

Patent Information:
Category(s):
Diagnostics
Oncology
For Information, Contact:
Katherine Pollard
Licensing Associate
The University of Toledo
419-530-6228
katherine.pollard@utoledo.edu
Inventors:
Mahasin Osman
William James
Keywords:
Drug-resistance
IQGAP1
Lung
Oncology
Triple negative breast cancer