Exercise Induced Myokines to Target Receptor Kinases and Chromatin Architecture

A Novel Myokine Oncology Therapeutic With Companion Drug Discovery Platform

NU 2019-094

INVENTORS

Hemant K. Roy

Vadim Backman*

SHORT DESCRIPTION

Novel oncology drug discovery platform using contraction-induced myokine secretion

BACKGROUND

Colorectal cancer is the third most commonly diagnosed cancer and second most common cause of cancer deaths in the United States. Despite its frequency, there are limited treatment options currently available. Regular physical exercise has been shown to lower the risk of colorectal cancer (CRC) by approximately 24%. This exercise effect is mediated, in part, by special proteins released by contracting skeletal muscles, termed myokines.

ABSTRACT

The current invention describes a system for the production, isolation and identification of contraction-induced myokines from muscle cells and demonstrates their efficaciousness in CRC cell lines. Myokine antineoplastic effects are demonstrated to occur through several mechanisms including; inhibition of tumor cell receptors specifically, the epidermal growth factor receptor (EGFR), transcriptional downregulation of proteins important for tumorigenesis in multiple types of cancer in specific, cyclo-oxygenase 2 (COX2) and alteration of chromatin structure which decreases phenotypic plasticity, improving drug response. Myokines are also shown to act synergistically with existing chemotherapeutics. Since the use of existing EGFR and COX-2 inhibitors is limited by toxicities and development of drug resistance, the myokine secretome offers an alternative platform for discovery of new sets of therapeutics for precision oncology. Moreover, the selectivity of myokines in altering chromatin nanoarchitecture makes them amenable to co-development with the Partial Wave Spectroscopic (PWS) diagnostic imaging test which detects nanomolecular changes in chromatin architecture. The PWS technology will help in; stratifying patients between responder and non responders, optimizing myokine dosage and improving the selection of synergizing chemotherapeutics.

APPLICATIONS

• Treatment of colorectal cancer
• Production, isolation and identification of myokines with antitumorigenic effects
• Monitoring myokine effects for improved selection of synergizing chemotherapeutics and dosage titration

ADVANTAGES

• Reduced toxicity compared to current therapeutics since they are made by the body
• Synergistic with existing chemotherapeutics
• Novel mechanisms of action

IP STATUS

Issued US Patent No. 11,560,414

Myokines normalize chromatin packing in colon cancer cells