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 G12C + STK11
Intermediate 0.50% Actionable B
KRAS G12C STK11
Clinical Implications

Very rare in CRC (<1%). STK11 co-mutation impact less studied in CRC than NSCLC. KRAS G12C inhibitors remain primary treatment.

Recommended
Sotorasib + PanitumumabAdagrasib + Cetuximab
Avoid
Immunotherapy alone
NTRK Fusion + Any
Intermediate 0.50% Actionable A
NTRK Fusion
Clinical Implications

Rare but highly actionable. TRK inhibitors are tumor-agnostic approved.

Recommended
LarotrectinibEntrectinib
NRG1 Fusion
Intermediate 0.30% Actionable Level 2B
NRG1 HER3
Rare but targetable. Zenocutuzumab shows promise.
Clinical Implications

Rare but targetable. Zenocutuzumab shows promise.

Requires RNA-based NGS detection.

Recommended
ZenocutuzumabClinical trials
MUTYH Polyposis
Intermediate 0.30% Actionable Level 2A
MUTYH
Autosomal recessive. Biallelic mutations needed.
Clinical Implications

Autosomal recessive. Biallelic mutations needed.

Recessive inheritance pattern.

Recommended
SurgerySurveillanceFamily testing
RET Fusion + Any
Intermediate 0.30% Actionable B
RET Fusion
Clinical Implications

Rare but actionable with selective RET inhibitors.

Recommended
SelpercatinibPralsetinib
KRAS G13D + HER2+
0.30% Actionable Level 2
KRAS HER2
Trastuzumab Deruxtecan (T-DXd) 5.4 mg/kg - DESTINY-CRC02 demonstrated efficacy regardless of KRAS status. ORR ~38% in RAS mutant patients. NOTE: Tucatinib + Trastuzumab (MOUNTAINEER) requires RAS wild-type, NOT appropriate here.
Clinical Implications

Trastuzumab Deruxtecan (T-DXd) 5.4 mg/kg - DESTINY-CRC02 demonstrated efficacy regardless of KRAS status. ORR ~38% in RAS mutant patients. NOTE: Tucatinib + Trastuzumab (MOUNTAINEER) requires RAS wild-type, NOT appropriate here.

Rare but actionable combination (<1% of mCRC). CRITICAL: Unlike other anti-HER2 approaches, T-DXd works in KRAS mutant tumors. DESTINY-CRC02 showed no difference in response between RAS WT and RAS mutant patients. Best results in IHC 3+. Monitor for ILD.

Recommended
Trastuzumab Deruxtecan (T-DXd) 5.4 mg/kgStandard chemotherapy + BevacizumabClinical trials
Avoid
Tucatinib + Trastuzumab (requires RAS WT)Anti-EGFR therapy
RET Fusion
Intermediate 0.20% Actionable Level 2A
RET
Very rare but highly actionable.
Clinical Implications

Very rare but highly actionable.

Identify through comprehensive NGS.

Recommended
SelpercatinibPralsetinib
ALK Fusion
Intermediate 0.10% Actionable Level 3
ALK
Extremely rare. Case reports of responses.
Clinical Implications

Extremely rare. Case reports of responses.

Identified incidentally on NGS.

Recommended
AlectinibLorlatinibCrizotinib
ROS1 Fusion
Intermediate 0.10% Actionable Level 3
ROS1
Ultra-rare. ROS1 inhibitors may help.
Clinical Implications

Ultra-rare. ROS1 inhibitors may help.

Entrectinib covers ROS1 and NTRK.

Recommended
EntrectinibCrizotinib
KRAS + APC
Intermediate 30.00% B
KRAS APC
Clinical Implications

Very common combination. APC loss is an early event in most CRCs.

Recommended
Standard chemotherapyBevacizumab-based
Avoid
Anti-EGFR monotherapy
KRAS + TP53
Intermediate 25.00% Level 2B
KRAS TP53
Most common combination. Standard RAS-mutant treatment.
Clinical Implications

Most common combination. Standard RAS-mutant treatment.

Consider intensive therapy if fit.

Recommended
FOLFOX + BevacizumabFOLFIRI + BevacizumabFOLFOXIRI + Bevacizumab
Avoid
Anti-EGFR
APC + KRAS + TP53
Intermediate 20.00% Level 2B
APC KRAS TP53
Classic Vogelstein adenoma-carcinoma sequence.
Clinical Implications

Classic Vogelstein adenoma-carcinoma sequence.

Canonical CRC development pathway.

Recommended
FOLFOX + BevacizumabFOLFIRI + Bevacizumab
Avoid
Anti-EGFR
RAS Mutant + Right-Sided
Poor 20.00% Level 2A
KRAS NRAS
Double negative prognostic factors. Aggressive biology.
Clinical Implications

Double negative prognostic factors. Aggressive biology.

Poor prognosis warrants aggressive approach.

Recommended
FOLFOXIRI + BevacizumabClinical trials
Avoid
Anti-EGFR
HER2-Low
Intermediate 15.00% Level 3
HER2
Emerging category. T-DXd trials ongoing in CRC.
Clinical Implications

Emerging category. T-DXd trials ongoing in CRC.

Keep patients in mind for emerging trials.

Recommended
Standard therapyClinical trials
TP53 Mutated (RAS WT)
Intermediate 15.00% Level 3
TP53
Does not preclude anti-EGFR if RAS/BRAF wild-type.
Clinical Implications

Does not preclude anti-EGFR if RAS/BRAF wild-type.

Prognosis depends on co-mutations.

Recommended
Anti-EGFR therapyStandard chemotherapy
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.