Expanding individualized therapeutic options via genoproteomics

Area of Science:

• Oncology
• Genomics
• Proteomics

Background:

• Clinical next-generation sequencing (NGS) identifies driver mutations for targeted cancer therapy.
• Patients lacking identifiable driver mutations have limited targeted treatment options.

Purpose of the Study:

• To evaluate the combined utility of NGS and proteomics for identifying actionable targets in diverse cancer types.
• To determine if a genoproteomic approach can expand therapeutic options for cancer patients.

Main Methods:

• Analyzed 169 formalin-fixed paraffin-embedded (FFPE) tumor samples (NSCLC, CRC, THCA, GC, GIST, MM) using NGS and proteomics.
• Identified actionable gene mutations via NGS and protein targets via proteomics.
• Validated a protein target (Map2k1) using MEK inhibitor in an in vivo lung tumor model.

Main Results:

• NGS detected actionable mutations in 43% of samples.
• Proteomics identified actionable targets in 72% of samples.
• Genoproteomics identified potential targets in 85% of patients, demonstrating MEK inhibitor efficacy in a preclinical model.

Conclusions:

• Combining NGS and proteomics significantly increases the identification of actionable targets for cancer therapy.
• Genoproteomics offers a promising strategy to broaden personalized treatment options, especially for patients without known driver mutations.
• Protein overexpression is a viable indicator for guiding targeted therapy selection.