Clinical cell-surface targets in metastatic and primary solid cancers.

Area of Science:

• Oncology
• Molecular Biology
• Immunotherapy

Background:

• Cell-surface target (CST) therapies are emerging for solid tumors.
• Current CST expression data primarily uses primary tumors, not metastatic disease where therapies are often applied.

Purpose of the Study:

• To comprehensively analyze CST expression across primary and metastatic solid tumors.
• To correlate RNA and protein expression for CSTs.
• To identify therapeutic opportunities and potential toxicities.

Main Methods:

• Assembled data from 818 clinical trials involving 78 CSTs.
• Analyzed RNA-seq and microarray data from over 30,000 benign, primary, and metastatic tumor samples.
• Utilized single-cell RNA-seq and matched RNA-protein expression data from various tissues and cell lines.

Main Results:

• High RNA expression accurately predicted high protein expression for CSTs across sample types.
• Detailed comparisons of metastatic versus primary tumor CST expression were made.
• Identified rare normal cell subpopulations potentially linked to toxicity.

Conclusions:

• This study provides a detailed landscape of CST expression in metastatic and primary cancers.
• Findings support the repositioning of CST therapies and development of bispecific approaches.
• The data aids in defining therapeutic strategies and mitigating toxicity.