EMID2 is a novel biotherapeutic for aggressive cancers identified by in vivo screening

Area of Science:

• Oncology
• Molecular Biology
• Biotechnology

Background:

• Most cancer drug candidates fail in clinical trials due to poor prediction of in vivo efficacy from preclinical screens.
• Current screening methods often lack the ability to accurately model the complex in vivo tumor environment.

Purpose of the Study:

• To develop and implement an in vivo screening strategy to identify novel protein therapeutics for cancer.
• To validate the therapeutic potential of identified candidates in preclinical cancer models.

Main Methods:

• Screened an Adeno-Associated Vector secretome library (>1000 clones) directly in vivo in a mouse cancer model.
• Validated the therapeutic effect of EMID2 in orthotopic and genetic models of lung and pancreatic cancer.

Main Results:

• EMID2 overexpression significantly inhibited tumor growth and metastatic dissemination in vivo.
• High EMID2 expression correlated with prolonged survival in aggressive human cancers.
• EMID2 functions by inhibiting TGFβ maturation and cancer-associated fibroblast activation, impacting the extracellular matrix and YAP signaling.

Conclusions:

• This study presents the first in vivo screening approach to identify proteins targeting cancer invasiveness.
• EMID2 emerged as a highly potent therapeutic candidate, highlighting the significance of the tumor extracellular matrix in controlling cancer dissemination.
• The findings underscore the potential of targeting the tumor microenvironment for effective cancer therapy.