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Multimodality imaging of the HER-kinase axis in cancer
Weibo Cai1, Gang Niu, Xiaoyuan Chen
1The Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford University School of Medicine, 1201 Welch Rd, P095, Stanford, CA 94305-5484, USA. shawchen@stanford.edu
Abstract:
The human epidermal growth factor receptor (HER) family of receptor tyrosine kinases controls critical pathways involved in epithelial cell differentiation, growth, division, and motility. Alterations and disruptions in the function of the HER-kinase axis can lead to malignancy. Many therapeutic agents targeting the HER-kinase axis are approved for clinical use or are in preclinical/clinical development. The ability to quantitatively image the HER-kinase axis in a noninvasive manner can aid in lesion detection, patient stratification, new drug development/validation, dose optimization, and treatment monitoring. This review summarizes the current status in multimodality imaging of the HER-kinase axis using PET, SPECT, optical, and MR imaging. The targeting ligands used include small-molecule tyrosine kinase inhibitors, peptides, proteins, antibodies, and engineered antibody fragments. EGFR and HER2 imaging have been well documented in the past, and imaging of HER3, HER4, HER heterodimers, and HER-kinase mutants deserves significant research effort in the future. Successful development of new HER-kinase-targeted imaging agents with optimal in vivo stability, targeting efficacy, and desirable pharmacokinetics for clinical translation will enable maximum benefit in cancer patient management.
Insights
Noninvasive imaging of the human epidermal growth factor receptor (HER) kinase axis aids cancer management. This review covers multimodality imaging techniques for HER-kinase targeted therapies and future research directions.
Area of Science:
- Oncology
- Molecular Imaging
- Biochemistry
Background:
- The human epidermal growth factor receptor (HER) family of receptor tyrosine kinases regulates vital cellular processes.
- Dysregulation of the HER-kinase axis is implicated in various malignancies.
- Targeted therapies for the HER-kinase axis are crucial in cancer treatment.
Purpose of the Study:
- To review the current state of multimodality imaging for the HER-kinase axis.
- To highlight the role of imaging in cancer detection, patient stratification, and treatment monitoring.
- To identify future research needs for developing novel HER-kinase imaging agents.
Main Methods:
- Review of current literature on PET, SPECT, optical, and MR imaging techniques targeting the HER-kinase axis.
- Analysis of various targeting ligands, including small molecules, peptides, proteins, and antibodies.
- Discussion of imaging applications in preclinical and clinical settings.
Main Results:
- Established imaging protocols exist for EGFR and HER2.
- Multimodality imaging offers quantitative assessment of HER-kinase axis activity.
- Targeting ligands vary, influencing imaging efficacy and pharmacokinetic profiles.
Conclusions:
- Noninvasive imaging of the HER-kinase axis is vital for personalized cancer management.
- Further research is needed for imaging HER3, HER4, heterodimers, and kinase mutants.
- Development of advanced imaging agents with improved stability and targeting is essential for clinical translation.
