Table 2.
Hallmarks of cancer and signaling pathways associated with specific resistance mechanisms.
| Top | Cytotoxic (N = 59) | Drugs Affected | % | Targeted therapies (N = 117) | Drugs Affected | % |
|---|---|---|---|---|---|---|
| 1 |
Metabolism (Detoxification transporters and enzymes, protection from ROS, increased glucose metabolism) |
21 | 36 |
Sustaining Proliferative Signaling (GF, Hedgehog, MAPK, PI3K, WNT, autophagy induction) |
65 | 56 |
| 2 |
Sustaining Proliferative Signaling (GF, Hedgehog, MAPK, PI3K, WNT, autophagy induction) |
19 | 32 |
Cell Death Evasion (BCL2 family, TP53, MDM2, PTEN, NF-KB, autophagy induction) |
41 | 35 |
| 3 |
Cell Death Evasion (BCL2 family, TP53, MDM2, PTEN, NF-KB, autophagy induction) |
10 | 17 |
Angiogenesis (EGF, IGF, FGF, VEGF, PDGF) |
31 | 26 |
| 4 |
Genome instability (TP53, MDM2, NHEJ, RAD51, CHEK1/2, BRCA1/2, HDAC) |
5 | 8 |
Metabolism (Detoxification transporters and enzymes, protection from ROS, increased glucose metabolism) |
21 | 18 |
| 5 |
Evading growth suppressors (TP53, RB, cyclins, CDKs, p16, p18, p21) |
4 | 7 |
Genome instability (TP53, MDM2, NHEJ, RAD51, CHEK1/2, BRCA1/2, HDAC, p21) |
18 | 15 |
| 6 |
Inflammation (NF-kB) |
4 | 7 |
Immune checkpoint (CD19, CD20, CTLA-4, NT5E, PCLP, PD-1, PD-L1) |
16 | 14 |
| 7 |
Angiogenesis (EGF, IGF, FGF, VEGF, PDGF) |
2 | 3 |
Evading growth suppressors (TP53, RB, cyclins, CDKs, p16, p18, p21) |
13 | 11 |
| 8 |
Immune checkpoint (CD19, CD20, CTLA-4, NT5E, PCLP, PD-1, PD-L1) |
0 | 0 |
EMT, invasion, and metastasis (EMT phenotype, integrin) |
13 | 11 |
| 9 |
EMT, invasion, and metastasis (EMT phenotype, integrin) |
0 | 0 |
Inflammation (NF-kB) |
12 | 10 |
| 10 |
Replicative immortality (WNT, Hedgehog, TERT) |
0 | 0 |
Replicative immortality (WNT, Hedgehog, TERT) |
8 | 7 |
N = FDA approved antineoplastic drugs available as at May 2019. Abbreviations: NF-κB—factor nuclear kappa B, TP53—tumor protein p53, MAPK—mitogen activated protein kinases, PI3K—phosphoinositide 3-kinase, EGF—epithelial growth factor, PTEN—phosphatase and tensin homolog, IGF—insulin-like growth factor 1, JAK—Janus kinase, STAT—signal transducer and activator of transcription, BCL2—B-cell lymphoma 2, FGF—fibroblast growth factor, ERBB2—erb-b2 receptor tyrosine kinase 2, HER2—human epidermal growth factor receptor 2, ROS—reactive oxygen species, GF—growth factor, NHEJ—non-homologous end joining, RAD51—RAD51 recombinase, CHEK1/2—checkpoint kinases 1 and 2, BRCA1/2—breast cancer type 1 susceptibility protein, and 2, HDAC—histone deacetylase, RB—retinoblastoma protein, CDKs—cyclin-dependent kinase, PDGF—platelet-derived growth factor, CTLA-4—cytotoxic T lymphocyte antigen 4, NT5E—ecto-5′-nucleotidase, PCLP—podocalyxin-like protein 1, PD-1—programmed cell death protein 1, PD-L1—programmed death-ligand 1, EMT—epithelial–mesenchymal transition, TERT—telomerase reverse transcriptase.