IRS2 as a driver of brain metastasis in colorectal cancer: A potential target for novel therapeutic strategies.

ABSTRACT:

Background

Colorectal cancer (CRC) ranks as the fourth most common cause of brain metastasis (BM), with its incidence on the rise. However, the molecular mechanisms driving the formation of these lesions from CRC remain unclear.

Methods

We analyzed the Foundation Medicine genomic database, which includes over 35,000 CRC samples from both local and metastatic sites. The role of insulin receptor substrate 2 (IRS2) in CRC brain tropism was investigated using various in vitro (co-culture systems and 3D sphere formation assays), in vivo (intracranial and subcutaneous mouse models), and ex vivo (CRC Patient-Derived Explants) models. The molecular and metabolic effects of IRS2 were examined through RNA sequencing and Seahorse analysis. The therapeutic potential of a combined treatm

SUBMITTER: Greenberg I 

PROVIDER: S-EPMC12417839 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature