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Glycoprotein Mucin 13 Expression as a Theranostic Target in Colorectal Cancer
Aiko Yamaguchi1, Ryan P Coll2, Jianbo Wang2
1Radiopharmaceuticals for Advanced Diagnostic Imaging and Therapy R&D Platform, Therapeutics Discovery Division, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Summary
Metastatic colorectal cancer (mCRC) shows high mortality. Mucin 13 (MUC13)-targeted radiopharmaceutical therapy (RPT) shows promise for mCRC treatment, with preclinical studies demonstrating efficacy and improved survival.
Area of Science:
- Oncology
- Nuclear Medicine
- Molecular Imaging
Background:
- Metastatic colorectal cancer (mCRC) has high mortality, necessitating novel therapies.
- Radiopharmaceutical therapy (RPT) offers targeted treatment for micrometastases.
- MUC13 is identified as a potential therapeutic target for mCRC.
Purpose of the Study:
- To evaluate Mucin 13 (MUC13) as a target for RPT in mCRC.
- To assess the preclinical efficacy of MUC13-targeted RPT using a monoclonal antibody.
Main Methods:
- Characterized MUC13 immunoreactivity and transcriptome in CRC patient samples (n=72 primary, 100 liver metastasis).
- Utilized a MUC13-targeted antibody (C14) labeled with 89Zr for PET imaging and 161Tb for RPT in preclinical mCRC mouse models.
Main Results:
- ~70% of mCRCs exhibited strong MUC13 immunoreactivity, inversely correlating with survival (P<0.01).
- PET imaging confirmed MUC13 expression, aligning with immunohistochemistry.
- MUC13-targeted RPT demonstrated in vivo efficacy and improved survival in preclinical models.
Conclusions:
- MUC13-targeted RPT efficacy is linked to radiopharmaceutical accumulation and DNA damage repair gene expression.
- A potential sensitivity signature for MUC13-positive mCRC theranostics was identified.
- Preclinical data support MUC13 as a viable target for mCRC RPT.
