Lessons to Learn for Adequate Targeted Therapy Development in Metastatic Colorectal Cancer Patients

Int J Mol Sci. 2021 May 9;22(9):5019. doi: 10.3390/ijms22095019.

Abstract

Insulin-like growth factor 1 receptor (IGF1R) is a receptor tyrosine kinase that regulates cell growth and proliferation. Upregulation of the IGF1R pathway constitutes a common paradigm shared with other receptor tyrosine kinases such as EGFR, HER2, and MET in different cancer types, including colon cancer. The main IGF1R signaling pathways are PI3K-AKT and MAPK-MEK. However, different processes, such as post-translational modification (SUMOylation), epithelial-to-mesenchymal transition (EMT), and microenvironment complexity, can also contribute to intrinsic and acquired resistance. Here, we discuss new strategies for adequate drug development in metastatic colorectal cancer patients.

Keywords: insulin-like growth factor receptor; metastatic colorectal cancer.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor
  • Colorectal Neoplasms / etiology
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Colorectal Neoplasms / therapy*
  • Drug Resistance, Neoplasm / drug effects
  • Epithelial-Mesenchymal Transition / drug effects
  • Humans
  • Liquid Biopsy
  • Molecular Targeted Therapy
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Protein Processing, Post-Translational
  • Receptor, IGF Type 1 / metabolism
  • Signal Transduction / drug effects
  • Treatment Outcome
  • Tumor Microenvironment / drug effects
  • ras Proteins / metabolism

Substances

  • Biomarkers, Tumor
  • IGF1R protein, human
  • Protein Kinase Inhibitors
  • Receptor, IGF Type 1
  • ras Proteins