Predictive value of CDC37 gene expression for targeted therapy in metastatic colorectal cancer

Area of Science:

• Oncology
• Molecular Biology
• Cancer Therapeutics

Background:

• CDC37 is crucial for HSP90-mediated client kinase recruitment.
• Kinase dependency on CDC37 may influence targeted therapy efficacy in metastatic colorectal cancer (mCRC).

Purpose of the Study:

• To investigate the association between CDC37 expression levels and treatment outcomes in mCRC patients.
• To explore the molecular profiles of CDC37-high versus CDC37-low mCRC.

Main Methods:

• Analysis of two independent mCRC cohorts (CALGB/SWOG 80405 and Japanese retrospective).
• Comparison of survival outcomes based on CDC37 expression (high vs. low).
• Molecular profiling of a large CRC dataset (N=10110) to characterize CDC37 expression groups.

Main Results:

• CDC37-high patients receiving bevacizumab showed significantly improved progression-free survival (PFS).
• CDC37-high patients receiving regorafenib demonstrated significantly better overall survival and PFS.
• No significant difference in outcomes was observed for CDC37-high versus CDC37-low patients treated with cetuximab.
• CDC37-high CRCs were linked to increased VEGFA, FLT1, KDR expression, and activated hypoxia signatures.

Conclusions:

• CDC37-high mCRC patients benefit more from anti-VEGF agents (bevacizumab, regorafenib) than from cetuximab.
• Tumor dependence on angiogenesis pathways is suggested in CDC37-high mCRC.