Table 3.

Potentially actionable targets and examples of their corresponding FDA-approved drugs(s)

Actionable geneExamples of FDA-approved drug(s)Potential actionability based on preclinical or clinical dataCommentReference(s)
ABL 1ImatinibClinicalThese drugs bind to the kinase domain of ABL and inhibit its activity.30
Dasatinib
Bosutinib
Nilotinib
Ponatinib
AKT1TemsirolimusPreclinicalTemsirolimus and everolimus are mTOR inhibitors.31
Everolimus
AKT2TemsirolimusPreclinicalTemsirolimus and everolimus are mTOR inhibitors.31
Everolimus
AKT3TemsirolimusPreclinicalTemsirolimus and everolimus are mTOR inhibitors.31
Everolimus
APCSulindacPreclinicalSulindac is an NSAID.32
ARBicalutamideClinicalBicalutamide and enzalutamide are androgen receptor inhibitors.33
Enzalutamide
ATMOlaparibPreclinicalOlaparib is a PARP inhibitor.34, 35
AXLCabozantinibPreclinicalCabozantinib is a multi-targeted kinase inhibitor.36
BCL2VenetoclaxPreclinicalVenetoclax is approved for the treatment of relapsed CLL.37, 38
BRAFDabrafenibClinicalVemurafenib and dabrafenib are BRAF inhibitors.39, 40
VemurafenibTrametinib and cobimetinib are MEK inhibitors.
Trametinib
Cobimetinib
BRCA2OlaparibClinicalOlaparib is a PARP inhibitor.35, 41
CCND1PalbociclibPreclinicalPalbociclib is a CDK4 and CDK6 inhibitor.42
CCND2PalbociclibPreclinicalPalbociclib is a CDK4 and CDK6 inhibitor42
CDK4PalbociclibPreclinicalPalbociclib is a CDK4 and CDK6 inhibitor.42
CCND3PalbociclibPreclinicalPalbociclib is a CDK4 and CDK6 inhibitor.42
CCKN2A/BPalbociclibPreclinicalPalbociclib is a CDK4 and CDK6 inhibitor.42
CRKLDasatinibPreclinicalDasatinib inhibits CRKL tyrosine phosphorylation.43
DMNT3AAzacitadinePreclinicalAzacitadine and decitabine are hypomethylating agents.44
Decitabine
EGFRErlotinibClinicalErlotinib, afatinib, and gefitinib are inhibitors of EGFR.45, 46
GefitinibCetuximab is a mAb that targets EGFR.
Afatinib
Cetuximab
ERRB2Ado-trastuzumab emtansineClinicalTrastuzumab and pertuzumab are mAbs targeting ERRB2.4, 47–49
TrastuzumabLapatinib and neratinib are multi-kinase inhibitors that inhibit both
PertuzumabEGFR and ERRB2.
Lapatinib
Neratinib
ESR1FulvestrantPreclinicalFulvestrant is a selective ER degrader.50
FANCAOlaparibPreclinicalOlaparib is a PARP inhibitor.35, 41, 51
FGF19LenvatinibPreclinicalFGF19 acts via FGFR1, FGFR2, FGFR3, and FGFR4.52
Pazopanib
Ponatinib
Regorafenib
FGF3LenvatinibPreclinicalFGF3 acts as a ligand for FGFR1, FGFR2, and possibly FGFR3.52
Pazopanib
Ponatinib
Regorafenib
FGF4LenvatinibPreclinicalFGF4 acts as a ligand for FGFR1, FGFR2, and possibly FGFR3.52
Pazopanib
Ponatinib
Regorafenib
FGFR1LenvatinibPreclinicalFGFR1 is a tyrosine kinase receptor.52
Pazopanib
Ponatinib
Regorafenib
FGFR2LenvatinibPreclinicalFGFR2 is a tyrosine kinase receptor.52
Pazopanib
Ponatinib
Regorafenib
FGFR4LenvatinibPreclinicalFGFR4 is a tyrosine kinase receptor.52
Pazopanib
Ponatinib
Regorafenib
FLT3SorafenibClinical forBoth sorafenib and sunitinib are multi-targeted kinase inhibitors.53, 54
Sunitinibmidostaurin and
Midostaurinpreclinical for other drugsMidostaurin is a multi-targeted kinase inhibitor that is approved for use in FLT3-mutated AML.
FLT4SorafenibPreclinicalFLT-4, also known as VEGFR3, is inhibited by the multi-targeted55
Pazopanibkinases listed.
Sunitinib
GNASTrametinibPreclinicalTrametinib is a MEK inhibitor.56
IDH1AzacitidinePreclinicalAzacitidine and decitabine are hypomethylating agents.57
Decitabine
IDH2AzacitidineClinical forAzacitidine and decitabine are hypomethylating agents.57
Decitabineenasidenib and
Enasidenibpreclinical for other drugs
JAK2RuxolitinibClinicalRuxolitinib is approved for the use in polycythemia vera and58, 59
Tofacitinibprimary myelofibrosis. Tofacitinib is approved for rheumatoid arthritis.
KRASTrametinibPreclinicalTrametinib is FDA approved for the treatment of melanoma and is a MEK inhibitor.56
MAP2K2TrametinibPreclinicalTrametinib is a MEK inhibitor.56
MCL1SorafenibPreclinicalSorafenib can inhibit MCL1.60
METCrizotinibPreclinicalCrizotinib and cabozantinib are MET inhibitors.61, 62
Cabozantinib
MSH2PembrolizumabNivolumabAtezolizumabClinicalThese drugs target PD-1 or PD-L1 and are often effective in patients with high tumor mutational burden due to mismatch repair gene defects.63
NF1TrametinibPreclinicalTemsirolimus and everolimus are mTOR inhibitors.64
Temsirolimus
Everolimus
NRASTrametinibPreclinicalTrametinib is a MEK inhibitor.56
PALB2OlaparibPreclinicalOlaparib is a PARP inhibitor.35, 41, 51
PIK3C2BTemsirolimusEverolimusCopanlisibClinical for copanlisib and preclinical for other drugsTemsirolimus and everolimus are mTOR inhibitors.31, 65
PIK3CATemsirolimusEverolimusClinical for copanlisib and preclinical for everolimusTemsirolimus and everolimus are mTOR inhibitors.31, 65
PTCH1VismodegibSonidegibClinicalBoth vismodegib and sonidegib are approved for the treatment of metastatic basal cell carcinoma.66, 67
PTENTemsirolimusPreclinicalTemsirolimus and everolimus are mTOR inhibitors.31, 68
Everolimus
RAF1RegorafenibPreclinicalRegorafenib is a multi-kinase inhibitor.69
ROS1CeritinibClinicalCeritinib and crizotinib are inhibitors of ROS1.46, 70
Crizotinib
RPTORTemsirolimusPreclinicalTemsirolimus and everolimus are mTOR inhibitors.31
Everolimus
SRCDasatinibPreclinicalDasatinib inhibits SRC.71
STK11DasatinibPreclinicalDasatinib is a multi-kinase inhibitor.72, 73
Everolimus
Temsirolimus
Bosutinib
TOP1IrinotecanPreclinicalIrinotecan and topotecan are topoisomerase I inhibitors.74, 75
Topotecan
TOP2DoxorubicinPreclinicalDoxorubicin and epirubicin inhibit topoisomerase II.76
Epirubicin
TP53BevacizumabPreclinicalBevacizumab (anti-VEGF-A antibody) has been associated with longer median PFS in TP53 mutant than in TP53 wild-type patients (11 vs. 5 months; retrospective study) and TP53 mutation is associated with increased VEGF-A.77–80
PazopanibIn patients with sarcoma, pazopanib (a VEGFR inhibitor) response is associated with the presence of TP53 mutations.
  • Abbreviation: PFS, progression-free survival.