Multimodal Approach for Identification and Validation of Hepatocellular Carcinoma Targets for Radiotheranostics.

Area of Science:

• Oncology
• Molecular Biology
• Biotechnology

Background:

• Hepatocellular carcinoma (HCC) lacks tumor-selective treatments despite advances in precision oncology.
• Identifying HCC-specific targets is crucial for developing targeted diagnostic and therapeutic agents.
• Current treatment options for HCC are limited in their selectivity.

Purpose of the Study:

• To identify and validate novel plasma membrane molecules overexpressed in HCC for targeted therapies.
• To develop HCC-selective diagnostic and therapeutic radiopharmaceuticals (radiotheranostics).
• To establish a multimodal approach for discovering and validating tumor-selective targets.

Main Methods:

• Integrated analysis of bulk and single-cell RNA sequencing data from HCC and normal liver samples.
• Immunohistochemical staining of tissue microarrays for target validation.
• Flow cytometry and western blot analysis to confirm target expression in HCC cell lines.
• Development and testing of novel antibody-based positron emission tomography (immunoPET) agents in murine models.

Main Results:

• Identification of several HCC-selective plasma membrane molecules.
• Validation of target selectivity through immunohistochemistry and cell line analysis.
• Successful development and preclinical testing of immunoPET agents targeting identified HCC markers.
• Demonstration of a multimodal pipeline for identifying and validating tumor-selective targets.

Conclusions:

• A multimodal approach effectively identifies and validates HCC-selective surface targets.
• Validated targets can be utilized for developing novel HCC-specific diagnostic and therapeutic radiopharmaceuticals.
• This strategy supports the advancement of precision oncology for hepatocellular carcinoma treatment.
• The identified targets hold potential for creating advanced radiotheranostic agents.