Druggable genetic alterations in different tumor types
| Target | Frequency of actionable mutations | Examples of targeted drugs |
|---|---|---|
| Lung cancer | ||
| EGFR ex19del, L858R | 10–20% in Europeans; 40–70% in Asians; more common in females and non-smokers | EGFR inhibitors (erlotinib, gefitinib, afatinib, osimertinib, etc.) |
| ALK fusions | 5%; more common in young patients, females, and non-smokers | ALK inhibitors (crizotinib, alectinib, lorlatinib, etc.) |
| RET fusions | 4%; more common in young patients, females, and non-smokers | RET inhibitors (selpercatinib, pralsetinib) |
| ROS1 fusions | 1.5–2%; more common in young patients, females, and non-smokers | ROS1 inhibitors (crizotinib, entrectinib, repotrectinib) |
| NTRK1-3 fusions | 0.2%; more common in young patients, females, and non-smokers | NTRK inhibitors (entrectinib, larotrectinib) |
| HER2 amplification | 1% | HER2 inhibitors (trastuzumab, pertuzumab) |
| HER2 exon 20 insertions | 2–3% | HER2 inhibitors (trastuzumab deruxtecan, pyrotinib) |
| MET exon 14 skipping | 2.5%; more common in elderly patients | MET inhibitors (capmatinib, tepotinib, crizotinib) |
| BRAF V600E, V600K, and other V600 mutations | 2% | BRAF inhibitors (vemurafenib, dabrafenib, encorafenib) in combination with MEK inhibitors |
| KRAS G12C | 10%; significantly more common in smokers | KRASG12C inhibitors (sotorasib, adagrasib) |
| Breast cancer | ||
| BRCA1/2 mutation | 7–10%; more common in patients with clinical signs of hereditary disease | Platinum compounds, PARP inhibitors (olaparib, talazoparib, niraparib, rucaparib) |
| PTEN mutation | 5% | AKT inhibitor (capivasertib) |
| PIK3CA mutation | 40% | AKT inhibitor (capivasertib), PI3K inhibitor (alpelisib) |
| AKT1 mutation | 4% | AKT inhibitor (capivasertib) |
| Ovarian cancer | ||
| BRCA1/2 mutation | 25–40% | Platinum compounds, mitomycin C, PARP inhibitors (olaparib, talazoparib, niraparib, rucaparib) |
| Colorectal cancer | ||
| BRAF V600E | 4–8% | BRAF inhibitor (encorafenib) plus EGFR inhibitor (cetuximab) |
| POLE mutation | < 1% | Immune checkpoint inhibitors (pembrolizumab, nivolumab, etc.) |
| HER2 amplification | 1–2% | HER2 inhibitors (trastuzumab, pertuzumab, lapatinib, etc.) |
| Pancreatic cancer | ||
| BRCA2 mutation | 2% | PARP inhibitors (olaparib, talazoparib, niraparib, rucaparib) |
| PALB2 mutation | 0.5% | PARP inhibitors (olaparib, talazoparib, niraparib, rucaparib) |
| KRAS G12C | 2% | KRASG12C inhibitors (sotorasib, adagrasib) |
| Biliary tract tumors | ||
| FGFR2 fusion or activating mutation | 20% | FGFR inhibitors (futibatinib, pemigatinib, infigratinib) |
| HER2 amplification or mutation | 4% | HER2 inhibitors (trastuzumab, pertuzumab, trastuzumab deruxtecan, pyrotinib) |
| BRAF V600E | 2% | BRAF inhibitors (vemurafenib, dabrafenib, encorafenib) in combination with MEK inhibitors |
| Melanoma | ||
| BRAF V600E | 60% | BRAF inhibitors (vemurafenib, dabrafenib, encorafenib) in combination with MEK inhibitors |
| KIT mutation | 15% in acral and mucosal melanomas | KIT inhibitors (imatinib, nilotinib, dasatinib) |
| Thyroid cancer | ||
| RET activating mutation | 10–25% of medullary carcinomas | RET inhibitors (selpercatinib, pralsetinib) |
| BRAF V600E | Up to 50% of papillary carcinomas | BRAF inhibitors (vemurafenib, dabrafenib, encorafenib) in combination with MEK inhibitors |
| RET fusion | 10% of papillary carcinomas | RET inhibitors (selpercatinib, pralsetinib) |
| Endometrial cancer | ||
| POLE mutation | 8% | Immune checkpoint inhibitors (pembrolizumab, nivolumab, etc.) |
| HER2 amplification | 10% | HER2 inhibitors (trastuzumab, pertuzumab) |
| Urothelial cancer | ||
| FGFR3 activating mutation | 15–20% | FGFR inhibitors (erdafitinib, futibatinib, pemigatinib, infigratinib) |
| HER2 amplification or mutation | 20–30% | HER2 inhibitors (trastuzumab, pertuzumab, trastuzumab deruxtecan, pyrotinib) |
EI: Conceptualization, Writing—original draft, Writing—review & editing. AS: Writing—review & editing. Both authors read and approved the submitted version.
Evgeny Imyanitov who is the Guest Editor of Exploration of Medicine had no involvement in the decision-making or the review process of this manuscript. The other author declares that there are no conflicts of interest.
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This work was supported by the Russian Science Foundation [21-75-30015]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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