Genomic Profiling of the Hallmarks of Cancer

Figures & data

Table 1. Summary of each hallmark of cancer and its associated genes, unique genes, and approved medications.

Hallmarks of Cancer	Unique Genes	All Associated Genes	Selected examples of FDA approved medications
Evasion of suppression of growth	AMER1, ATP2B3, AXIN2, BCOR, CAMTA1, EBF1, FCGR2 B, PDCD1LG2, PHOX2B, PTPRT, TSC1, TSC2, ZFHX3	ABI1, AKT1, AMER1, APC, ARID1A, ARID2, ATP2B3, ATR, AXIN1, AXIN2, BCOR, BLM, CAMTA1, CBFA2T3, CBLB, CCDC6, CDC73, CDKN2A, CIC, CNOT3, CTNNB1, CUX1, CYLD, DDX10, DDX3X, EBF1, ELF4, ELL, EP300, EPAS1, ERBB4, ESR1, FAT1, FAT4, FCGR2B, FLT3, FUS, GNAS, GPC3, GRIN2A, HNF1A, HOXA11, KLF4, KMT2C, LATS1, LATS2, LRP1B, MEN1, NCOR2, NDRG1, NF1, NF2, NOTCH2, PAX3, PDCD1LG2, PER1, PHOX2B, PIK3R1, PMS2, PPARG, PTEN, PTK6, PTPRT, QKI, RABEP1, RB1, RBM10, RHOA, RHOH, RNF43, RUNX1T1, SMAD2, SMAD3, SPOP, TBL1XR1, TET1, TGFBR2, TP53, TSC1, TSC2, VHL, ZFHX3	TSC1,TSC2: everolimus
Genome instability and mutations	ATRX, BRIP1, CHD4, CLTC, CTCF, ERCC4, EWSR1, FBXW 7, LMNA, POT1, PPP6C, RANBP2	ABL1, AKT1, APC, APOBEC3B, ARID1A, ARID2, ATM, ATR, ATRX, BAP1, BCL10, BCL9L, BLM, BRCA1, BRCA2, BRIP1, BTK, BUB1B, CASC5, CC DC6, CCND1, CDK12, CHD4, CHEK2, CLTC, CREBBP, CTCF, CTNNB1, CUX1, DAXX, DDB2, DICER1, ERCC2, ERCC3, ERCC4, ERCC5, EWSR1, FANCD2, FBXW7, FHIT, HRAS, KMT2C, LATS1, LATS2, LMNA, MED12, MYC, NCOR2, PBRM1, PIK3CB, PMS2, POT1, PPM1D, PPP6C, PSIP1, PTEN, RAC1, RAD21, RANBP2, RB1, RECQL4, RHOA, SIX1, SPOP, STAG2, TERT, TP53, UBR5, USP8	ABL1: imatinib, dasatinib, nilotinib. BRCA1, BRCA2: rucaparib, niraparib.
Escaping immune response	B2M, CIITA	B2M, CBLB, CIITA, CTNNB1, CUX1, EGFR, ESR1, HIF1A, HRAS, JAK1, MYC, PTEN, RAC1, RB1, TNFAIP3, TP53	EGFR: erlotinib, gefitinib, afatinib, osimertinib, dacomitinib.
Cell replicative immortality	BCL11A, CDK4, MLLT10, WIF1, ZBTB16	ARID1A, ATM, AXIN1, BCL11A, BRD4, BTK, CCNE1, CDK4, CTNNB1, DICER1, ELF4, ELL, ERG, FAS, FGFR1, HEY1, KDR, KLF4, KMT2C, KMT2D, KRAS, MLLT10, MYC, NDRG1, NOTCH1, NRAS, PIK3R1, POU5F1, PTEN, RNF43, SIX1, SLC34A2, SMAD2, STAG2, TERT, TP53, WIF1, ZBTB16	KRAS, (wild type): cetuximab, panitumumab, regorafenib.
Activating invasion and metastasis	BCORL1, BMPR1A, CBFB, CCNB1IP1, CLTCL1, DDR2, G AS7, LIFR, PREX2, WAS	ABI1, ABL1, ACKR3, ACVR1, AFF4, AKT1, ALK, APC, ARID1A, ARNT, ATM, ATP1A1, BAP1, BCL10, BCL9, BCL9L, BCORL1, BMPR1A, BRCA1, BUB1B, CALR, CASP8, CBFB, CBL, CBLB, CCNB1IP1, CCND1, CD79A, CDC73, CDH1, CDH11, CDKN2A, CIC, CLTCL1, CNBP, CREB3L1, CREBBP, CTNNB1, CUX1, CXCR4, CYLD, DAXX, DDB2, DDR2, DDX3X, DDX5, DICER1, DNM2, EGFR, EIF3E, EPAS1, ERBB2, ERBB3, ESR1, ETV6, EZR, FANCD2, FAS, FAT1, FAT4, FBXO11, FGFR1, FGFR2, FGFR4, FHIT, FLT4, FOXA1, FUBP1, FUS, GAS7, GPC3, GRIN2A, HIF1A, HNF1A, HNRNPA2B1, HOXA11, HRAS, KDM6A, KDR, KIT, KLF4, KMT2C, KMT2D, KRAS, LATS2, LEF1, LIFR, LRP1B, MAPK1, MED12, MTOR, MYC, MYD88, NDRG1, NF1, NF2, NONO, NOTCH2, NRAS, PAX3, PAX5, PAX7, PAX8, PBRM1, PHOX2B, PIK3CA, PIK3R1, PIM1, PLCG1, PMS2, POU5F1, PREX2, PRKAR1A, PSIP1, PTEN, PTK6, PTPN13, RABEP1, RAC1, RAD21, RAF1, RAP1GDS1, RB1, RECQL4, RHOA, RHOH, , SLC34A2, SIX1, SMAD2, SMAD3, SPOP, SUZ12, TBL1XR1, TCF7L2, TERT, TET1, TGFBR2, TP53, TP63, UBR5, VHL, WAS	ABL1: imatinib, dasatinib, nilotinib ALK: crizotinib, ceritinib, alectinib, lorlatinib, brigatinib. BRCA1, BRCA2: rucaparib, niraparib EGFR: Erlotinib, gefitinib, afatinib, osimertinib, dacomitinib ERBB2: trastuzumab, ado-trastuzumab emtansine, lapatinib, pertuzumab+trastuzumab, lapatinib+trastuzumab, neratinib FGFR2: erdafitinib KIT: regorafenib, imatinib, sunitinib KRAS, (wild type): cetuximab, panitumumab, regorafenib
Escaping programmed cell death	BIRC3, CARD11, CARS, CD79B, ETNK1, FCGR2B, HIP1, K EAP1, PRDM16, SFPQ, TRAF7	ABL1, ACKR3, ACVR1, AKT1, ALK, APC, AR, ARID1A, ATM, ATP1A1, ATR, AXIN1, BAP1, BCL10, BIRC3, BLM, BRAF, BRCA1, BRCA2, BRD4, BTK, BUB1B, CALR, CARD11, CARS, CASC5, CASP8, CCDC6, CD79B, CDC73, CDH11, CDKN2A, CHEK2, CNBP, CNOT3, CREBBP, CTNNB1, CUX1, CYLD, DAXX, DDB2, DDIT3, DDX3X, DDX5, DDX6, DICER1, EGFR, EIF3E, ELF4, ELK4, EP300, EPAS1, ERBB2, ERBB3, ERBB4, ERCC2, ERCC3, ERCC5, ETNK1, ETV6, EZR, FANCD2, FAS, FAT1, FBXO11, FCGR2B, FGFR2, FGFR3, FLT3, FLT4, FUBP1, HIF1A, HIP1, HNF1A, HNRNPA2B1, HOXA11, HRAS, JAK1, JAK2, KEAP1, KIT, KLF4, KRAS, LATS1, LATS2, LCK, MAPK1, MEN1, MTOR, MYC, MYD88, NCOR2, NF1, NFE2L2, NOTCH1, NOTCH2, NRAS, NT5C2, PAX3, PAX5, PAX8, PBRM1, PBX1, PER1, PIK3CA, PIK3CB, PIM1, PLCG1, PMS2, PPM1D, PRDM16, PRKACA, PRKAR1A, PSIP1, PTEN, PTK6, PTPN13, QKI, RAC1, RAD21, RAF1, RB1, RBM10, RECQL4, RHOA, RHOH, RNF43, SFPQ, SIX1, SMAD2, SMAD3, SPOP, TCF7L2, TCL1A, TERT, TET1, TP53, TP63, TRAF7, UBR5, VHL, XPO1	ABL1: imatinib, dasatinib, nilotinib ALK: crizotinib, ceritinib, alectinib, lorlatinib, brigatinib BRAF: vemurafenib+cobimetinib, dabrafenib+trametinib, binimetinib+encorafenib BRCA1, BRCA2: rucaparib, niraparib EGFR: erlotinib, gefitinib, afatinib, osimertinib, dacomitinib ERBB2: trastuzumab, ado-trastuzumab emtansine, lapatinib, pertuzumab+trastuzumab, lapatinib+trastuzumab, neratinib. FGFR2, FGFR3: erdafitinib KIT: regorafenib, imatinib, sunitinib KRAS, (wild type): cetuximab, panitumumab, regorafenib
Proliferative signaling	CACNA1D, CCND2, CDK6, CREB3L2, CRTC1, EPS15, GN A11, GNAQ, JAK3, MAP3K13, NTRK1, NTRK2, NTRK3, ROS1	ABI1, ABL1, ACKR3, ACVR1, AFF4, AKT1, ALK, AR, BAP1, BCL10, BCL9, BCL9L, BRAF, BRD4, BUB1B, CACNA1D, CALR, CASP8, CBL, CCND2, CCNE1, CD79A, CDK6, CREB3L2, CREBBP, CRTC1, CTNNB1, CUX1, CXCR4, DAXX, DDB2, DDX5, DDX6, DICER1, DNM2, EGFR, EIF3E, ELF4, ELK4, EPAS1, EPS15, ERBB2, ERBB3, ERBB4, ESR1, EZR, FANCD2, FAS, FBXO11, FGFR1, FGFR2, FGFR3, FGFR4, FLT3, FLT4, FOXA1, FUBP1, GNA11, GNAQ, GNAS, GRIN2A, HEY1, HNRNPA2B1, HOXA11, HRAS, IL6ST, JAK1, JAK2, JAK3, KDM6A, KDR, KIT, KLF4, KMT2C, KMT2D, KRAS, LCK, LEF1, MAP3K13, MED12, MEN1, MTOR, MYC, MYD88, NDRG1, NONO, NOTCH1, NOTCH2, NRAS, NT5C2, NTRK1, NTRK2, NTRK3, PAX3, PAX5, PAX7, PAX8, PIK3CA, PIM1, PLCG1, POU2AF1, POU5F1, PPARG, PPM1D, PRKACA, PRKAR1A, PTK6, RAC1, RAF1, RAP1GDS1, ROS1, SIX1, SLC34A2, SMAD3, SUZ12, TBL1XR1, TCF7L2, TCL1A, TERT, TP63, UBR5, XPO1	ABL1: imatinib, dasatinib, nilotinib. BRAF: vemurafenib+cobimetinib, dabrafenib+trametinib, binimetinib+encorafenib EGFR: erlotinib, gefitinib, afatinib, osimertinib, dacomitinib ERBB2: trastuzumab, ado-trastuzumab emtansine, lapatinib, pertuzumab+trastuzumab, lapatinib+trastuzumab, neratinib FGFR2, FGFR3: erdafitinib KIT: regorafenib, imatinib, sunitinib KRAS, (wild type): cetuximab, panitumumab, regorafenib NTRK1, NTRK2, NTRK3, (fusions): larotrectinib ROS1: crizotinib
Change of cellular energetics	IDH1, IDH2, PAFAH1B2, PICALM, TFE3	ABL1, AKT1, ARNT, ATR, BAP1, BRCA1, CBFA2T3, CCDC6, CCND1, CDH1, CDK12, CIC, CTNNB1, DDX3X, EGFR, ERBB2, HIF1A, IDH1, IDH2, JAK2, KMT2D, KRAS, MAPK1, MTOR, MYC, NF2, NFE2L2, NONO, NOTCH1, PAFAH1B2, PBRM1, PBX1, PICALM, PIM1, PPARG, PTEN, RB1, SDHA, SIX1, TFE3, TP53, USP8, VHL	ABL1: imatinib, dasatinib, nilotinib. BRCA1, BRCA2: rucaparib, niraparib. EGFR: erlotinib, gefitinib, afatinib, osimertinib, dacomitinib. ERBB2: trastuzumab, ado-trastuzumab emtansine, lapatinib, pertuzumab+trastuzumab, lapatinib+trastuzumab, neratinib. IDH1: ivosidenib IDH2: enasidenib KRAS, (wild type): cetuximab, panitumumab, regorafenib.
Angiogenesis	NAB2, RNF213	ABL1, ACKR3, AKT1, ARNT, BCL9, BRCA1, CALR, CASP8, CDKN2A, CREB3L1, CTNNB1, CUX1, CYLD, DDX6, DICER1, DNM2, EGFR, EIF3E, ELL, EPAS1, HIF1A, HRAS, KDR, KRAS, LCK, MTOR, MYC, NAB2, NF1, NOTCH1, PBX1, PIK3CA, PIM1, PLCG1, RAC1, RAF1, RNF213, RUNX1T1, SDHA, SIX1, TERT, TP53, UBR5, VHL	ABL1: imatinib, dasatinib, nilotinib BRCA1, BRCA2: rucaparib, niraparib EGFR: erlotinib, gefitinib, afatinib, osimertinib, dacomitinib. KRAS, (wild type): cetuximab, panitumumab, regorafenib
Promoting inflammation	none	APOBEC3B, ATM, CASP8, CYLD, DDIT3, EPAS1, FANCD2, HNRNPA2B1, HRAS, IL6ST, JAK2, KDR, KRAS, MYD88, PBRM1, RHOA, TNFAIP3, TP53	JAK2: ruxolitinib KRAS, (wild type): cetuximab, panitumumab, regorafenib.

Figure 1. Schematic summary of the different interactions leading to establishment and maintenance of dormancy versus breaking dormancy and activating proliferation