Targeting the formation of aggressive cancer-associated fibroblasts for metastasis inhibition in solid tumors

This technology uses computational methods to identify the cell of origin and differentiation path leading to the formation of a particular type of cancer-associated fibroblasts (“aCAFs,” standing for aggressive cancer-associated fibroblasts), as well as related pan-cancer targets for therapeutic development.

Unmet Need: Pan-cancer therapeutics inhibiting the formation of COL11A1-expressing cancer-associated fibroblasts

COL11A1 is a prominent marker of a pan-cancer gene signature in a particular type (aCAFs) of cancer associated fibroblasts activated at advanced stages of different tumors. Experimental evidence suggests that CAFs modulate the tumor microenvironment, but their origin and underlying biological mechanisms remain unclear. Understanding the role of aCAFs in cancer prognosis and metastasis will enable the development of therapeutics and diagnostic tools for various solid tumors.

The Technology: Origin and cellular transition leading to the formation of aCAFs

This technology identifies a type of adipose-derived stromal cells (ASCs) that can transform into aCAFs following interaction of cancer cells with the adipose microenvironment. It uses RNA sequencing and computational methods to demonstrate the continuous transition of the gene signature of ASCs into the aCAF signature. This technology identifies potential pan-cancer metastasis-inhibiting targets for therapeutic development, prominent among which is long noncoding RNA LINC01614 and protein-coding genes such as THBS2 and SFRP4.

Applications:

• Diagnosis of solid tumors
• Therapeutics for cancers inhibiting progression to advanced stages
• Immunotherapy for cancer treatment
• Modulation of adipose tissue composition
• Research tool to study the mechanism of cancer metastasis

Advantages:

• Unbiased computational method to identify therapeutic targets for cancer
• More targeted cancer immunotherapy
• Provides understanding of disease mechanism
• Can be used to develop metastasis-inhibiting therapy

Lead Inventor:

Dimitris Anastassiou, Ph.D.

Patent Information:

Patent Pending

Related Publications:

• Zhu K, Cai L, Cui C, de Los Toyos JR, Anastassiou D. “Single-cell analysis reveals the pan-cancer invasiveness-associated transition of adipose-derived stromal cells into COL11A1-expressing cancer-associated fibroblasts” PLoS Comput Biol. 2021 Jul 20; 17(7): e1009228.

Tech Ventures Reference:

• IR CU21079

• Licensing Contact: Jerry Kokoskha