Mutation Combinations Database
Comprehensive guide to genetic mutation combinations in colorectal cancer, their clinical implications, and treatment recommendations.
Clinical Implications
Most common KRAS. MRTX1133 and other G12D inhibitors in development.
Watch for G12D inhibitor approvals 2024-2025.
Recommended
Avoid
Clinical Implications
SMAD4 loss = poor prognosis, liver mets.
Aggressive treatment warranted.
Recommended
Clinical Implications
MRTX1133 and others showing promise. Could transform treatment.
G12D inhibitors 1-2 years behind G12C.
Recommended
Clinical Implications
KRAS G12D is not yet targetable with approved drugs. Clinical trials for G12D inhibitors ongoing.
Recommended
Avoid
Clinical Implications
Activates PI3K pathway. Mixed data on anti-EGFR resistance.
May inform aspirin use.
Recommended
Clinical Implications
Second most common KRAS. No specific inhibitor yet.
May have slightly worse prognosis than G12D.
Recommended
Avoid
Clinical Implications
PI3K pathway activation. Aspirin benefit unclear for exon 9.
Different biology than exon 20.
Recommended
Clinical Implications
Standard chemotherapy backbone. Anti-EGFR controversy: Retrospective data (De Roock 2010, PMID: 20619739) suggested possible cetuximab sensitivity, but ICECREAM study did not confirm benefit. NOT recommended for anti-EGFR outside trials. If HER2 co-amplified, consider T-DXd.
KRAS G13D represents ~7% of mCRC. Prognosis intermediate between KRAS WT and G12 mutations. Historical controversy about cetuximab sensitivity not confirmed prospectively. If HER2 co-amplified, consider T-DXd (DESTINY-CRC02).
Recommended
Avoid
Clinical Implications
Functionally equivalent to KRAS. Precludes anti-EGFR.
Must test both KRAS and NRAS.
Recommended
Avoid
Clinical Implications
Dual pathway activation = aggressive biology.
Consider aspirin for PIK3CA component.
Recommended
Avoid
Clinical Implications
Bypass resistance to anti-EGFR. Consider combo strategies.
Check MET on anti-EGFR progression.
Recommended
Avoid
Clinical Implications
Standard chemotherapy + Bevacizumab. Anti-EGFR not indicated. If HER2 co-amplified, consider Trastuzumab Deruxtecan (DESTINY-CRC02 showed efficacy in RAS mutant). TP53 mutations do not currently guide therapy selection.
Co-occurrence of KRAS G13D and TP53 mutation seen in ~5% of mCRC. TP53 dysfunction may reduce chemotherapy sensitivity but is not therapeutically actionable. Focus on KRAS-driven treatment selection. Test for HER2 amplification as potential targetable co-alteration.
Recommended
Avoid
Clinical Implications
Less common KRAS mutations. Confirmed anti-EGFR resistance.
Always test extended RAS panel.
Recommended
Avoid
Clinical Implications
Double PI3K pathway activation. May benefit from PI3K pathway inhibitors in trials.
Recommended
Clinical Implications
WRN helicase essential in MSI-H. Synthetic lethal approach.
Multiple WRN inhibitors in early trials.
Recommended
About This Database
This database contains clinically relevant mutation combinations in colorectal cancer. Each combination includes:
- Genes involved - The genetic alterations present
- Prognosis - Expected outcome classification
- Prevalence - How common in CRC patients
- Recommended treatments - Evidence-based options
- Treatments to avoid - Known ineffective therapies
- Evidence level - Strength of supporting data
Actionable combinations have FDA-approved targeted therapies or strong clinical trial evidence. Always consult with your oncologist for personalized treatment decisions.