Mutation Combinations Database

Comprehensive guide to genetic mutation combinations in colorectal cancer, their clinical implications, and treatment recommendations.

64
Total Combinations
39
Actionable Targets
14
Categories
Showing 64 combinations
KRAS G12D + TP53
Intermediate
KRAS G12D TP53
12.00% prevalence

Recommended
Standard chemotherapy G12D inhibitors (trials)
Avoid
Anti-EGFR therapy
General
B
PTEN Loss
Intermediate
PTEN
10.00% prevalence

Activates PI3K pathway. Mixed data on anti-EGFR resistance.

Recommended
Standard therapy Consider aspirin
PIK3CA Pathway
Level 3
KRAS G12V
Intermediate
KRAS
8.00% prevalence

Second most common KRAS. No specific inhibitor yet.

Recommended
FOLFOX + Bevacizumab FOLFIRI + Bevacizumab
Avoid
Anti-EGFR
RAS Pathway
Level 2A
PIK3CA Exon 9
Intermediate
PIK3CA
8.00% prevalence

PI3K pathway activation. Aspirin benefit unclear for exon 9.

Recommended
Standard chemotherapy Clinical trials
PIK3CA Pathway
Level 3
KRAS G13D
KRAS
7.00% prevalence

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.

Recommended
FOLFOX/FOLFIRI + Bevacizumab FOLFOXIRI + Bevacizumab TAS-102 + Bevacizumab (third-line)
Avoid
Anti-EGFR
RAS Pathway
Level 2A
NRAS Mutated
Intermediate
NRAS
5.00% prevalence

Functionally equivalent to KRAS. Precludes anti-EGFR.

Recommended
FOLFOX + Bevacizumab FOLFIRI + Bevacizumab FOLFOXIRI + Bevacizumab
Avoid
Cetuximab Panitumumab
RAS Pathway
Level 1
PIK3CA + KRAS
Poor
PIK3CA KRAS
5.00% prevalence

Dual pathway activation = aggressive biology.

Recommended
Intensive chemotherapy Clinical trials
Avoid
Anti-EGFR
PIK3CA Pathway
Level 3
MET Amp (Acquired)
Poor
MET
5.00% prevalence

Bypass resistance to anti-EGFR. Consider combo strategies.

Recommended
Clinical trials (MET + EGFR) Alternative chemo
Avoid
Anti-EGFR alone
Resistance Mechanisms
Level 3
KRAS G13D + TP53
KRAS TP53
5.00% prevalence

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.

Recommended
FOLFOX/FOLFIRI + Bevacizumab FOLFOXIRI + Bevacizumab TAS-102 + Bevacizumab +1 more
Avoid
Anti-EGFR monoclonal antibodies
RAS Pathway
Level 3
KRAS Codon 61/146
Intermediate
KRAS
4.00% prevalence

Less common KRAS mutations. Confirmed anti-EGFR resistance.

Recommended
FOLFOX + Bevacizumab FOLFIRI + Bevacizumab
Avoid
Anti-EGFR
RAS Pathway
Level 1
PTEN Loss + PIK3CA
Intermediate
PTEN Loss PIK3CA
4.00% prevalence

Recommended
Standard chemotherapy PI3K inhibitors (trials)
General
C
WRN Deficient (MSI-H)
Good
WRN
3.00% prevalence

WRN helicase essential in MSI-H. Synthetic lethal approach.

Recommended
Immunotherapy WRN inhibitor trials
Emerging Targets
Level 3
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.