Table 1.
Examples of somatic predictors for response to anti-cancer drugs approved by the US FDA (Non-standard abbreviations: EGFR=epidermal growth factor receptor, PCR=polymerase chain reaction, HPLC=high performance liquid chromatography, FISH=fluorescent in situ hybridization, IHC=immunohistochemistry, MGMT=O6-methylguanine–DNA methyltransferase, PDGFR=platelet derived growth factor receptor, ER=estrogen receptor, PR=progesterone receptor, HER2=Human epidermal growth factor receptor 2)
| Target | Drugs | Tumours | Markers | Test | Significance |
|---|---|---|---|---|---|
| EGFR | Cetuximab Panitumumab |
Colorectal | KRAS mutations at codon 12, 13, 61 and 146 | Direct sequencing or commercial kits available eg DxS Therascreen KRAS mutation test kit (PCR) | Resistance(98) |
| BRAF mutations at exon 11, 15, (V600E) | Direct sequencing or commercial kits available, eg DxS BRAF mutation test kit (PCR) | Resistance(98) | |||
| IHC not commonly used to predict for response for cetuximab | Response(99) | ||||
| Cetuximab | Lung | EGFR gene copy number | FISH | Response(100) | |
| EGFR | Gefitinib Erlotinib |
Lung | EGFR mutations include exon 19 deletions, exon 18 (G719A/C/S), exon 21 (L858R, L861Q) | Direct sequencing, denaturing HPLC, length analysis, PCR-based assays such as Amplification Refractory Mutation System ARMS® | Response(12) |
| Exon 20 mutations T790M and insertion | Resistance(12) | ||||
| EGFR gene copy number | FISH | Response(101) | |||
| CD20 | Rituximab Ibritumomab tiuxetan |
B cell Non Hodgkin’s Lymphoma | CD 20 | IHC | Response(102,103) |
| CD52 | Alemtuzumab | Chronic Lymphocytic Leukemia | CD 52 | IHC | Response(104) |
| MGMT | Temozolomide | Glioblastoma Multiforme | MGMT methylation | Methylation specific PCR | Response(39) |
| Bcl-abl, KIT, PDGFR | Imatinib | Gastrointestinal stromal tumor, Chronic Myeloid Leukemia(106) | CD 117 | IHC | Response(105,107) |
| KIT mutations | Direct sequencing, denaturing HPLC | ||||
| Exon 11 | Longer duration of response(107) | ||||
| Exon 9 | Relative resistance(107) | ||||
| Exon 13, 17 | Resistance(107) | ||||
| PDGFRA mutation | |||||
| Exon 18(D842V) | Sensitive(107) | ||||
| Exon 12, 14 | Resistance(107) | ||||
| ER/PR | Tamoxifen Anastrozole Letrozole Exemestane Fulvestrant |
Breast | ER/PR | IHC | Response(108) |
| HER2 | Trastuzumab | Breast Stomach |
HER2 | IHC 3+/FISH | Response(109–111) |
| Lapatinib | Breast |