Consensus molecular subtypes and the evolution of precision medicine in colorectal cancer

Area of Science:

• Oncology
• Genomics
• Pharmacology

Background:

• Colorectal cancer (CRC) targeted therapies, initially based on a 'one gene, one drug' model, are impacted by genomic events.
• Understanding CRC's complex genome and clonal evolution under treatment is crucial.
• Pharmacodynamic effects of target inhibition highlight treatment complexities.

Purpose of the Study:

• To advocate for a shift in CRC therapeutic strategies.
• To emphasize the need for a 'multi-gene, multi-drug' approach.
• To promote a 'multi-molecular' perspective in CRC therapy development.

Main Methods:

• Reviewing current knowledge on CRC genomic drivers.
• Analyzing clonal evolution patterns under treatment pressure.
• Characterizing transcriptomic subtypes of CRC, including tumor, stromal, and immune components.

Main Results:

• Genomic events critically influence response to targeted CRC therapies.
• Convergent pathway dependencies are revealed through transcriptomic subtyping.
• A 'multi-gene, multi-drug' model is supported by current data.

Conclusions:

• The 'one gene, one drug' paradigm is insufficient for optimal CRC treatment.
• A 'multi-gene, multi-drug' approach is necessary for effective therapeutic decisions in CRC.
• A 'multi-molecular' perspective is essential for developing future CRC therapies.