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Table 1 Anti-cancer drugs for targeted therapy

From: Targeted therapy: resistance and re-sensitization

Target First-line drug(s) Principal indication(s) Potential resistance mechanism(s) Re-sensitization agent(s) References
BCR-ABL fusion Imatinib CML Fixing the kinase domain in its active configuration 1. Dasatinib
2. Nilotinib
3. Ponatinib
[7, 8]
KIT Imatinib GIST
Melanoma
Sarcoma
1. Mutations of c-KIT axons 9/11
2. PDGFRA (D842 V) mutation
1. Sunitinib
2. Regorafenib
[7, 8]
EGFR Gefitinib
Erlotinib
Cetuximab
NSCLC
Colorectal cancer
1. Secondary mutations in EGFR such as T790 M “gatekeeper” mutation
2. Multi-signaling cascade-driven disorders
3. EGFR S492R mutation
1. Cetuximab + Afatinid
2. Rociletinib
3. Panitumumab
[913]
ALK rearrangement Crizotinib NSCLC Secondary mutations in ALK rearrangement Ceritinib
Alertinib
[14, 15]
HER2 Trastuzumab Breast cancer
Gastric cancer
1. Lack of the extracellular domain of HER2
2. Enhanced Her2 dimerization
1. Pertuzumab
2. Herceptin emtansine
3. Lapatinib
[16, 17]
VEGF/VEGFR Bevacizumab
Ramucirumab
Sorafenib
Sunitinib
Aflibercept
Pazopanib
Vandetanib
Vatalanib
Cediranib
Axitinib
Renal cancer
Colorectal cancer
Small cell lung cancer
Thyroid cancer
Sarcoma
1. Alternative angiogenic signaling
2. Increased HIF1, MDSCs, CSCs, etc.
1. Alternative angiogenic inhibitors
2. CSC inhibitors
[1821]
BRAF Vemurafenib
Dabrafenib
Melanoma 1. BRAF amplification and new BRAF V600E splice isoforms
2. BRAF-independent MAPK activation
1. Vemurafenib + Cobimetinib
2. Dabrafenib + Trametinib
3. Anti-PD-1/PD-L1 antibodies
[2224]
  1. BCR-ABL breakpoint cluster region-Abelson, CML chronic myeloid leukemia, KIT kit receptor tyrosine kinase, GIST gastrointestinal stromal tumor, PDGFRA platelet-derived growth factor receptor A, EGFR epidermal growth factor receptor, NSCLC non–small cell lung cancer, ALK anaplastic lymphoma kinase, HER2 human EGFR2, VEGF(R) vascular endothelial cell growth factor (receptor), HIF1 hypoxia-inducible factor 1, MDSC myeloid-derived suppressor cell, CSC cancer stem cell, BRAF raf murine sarcoma viral oncogene homolog B, MAPK mitogen-activated protein kinase, PD-1 programmed cell death protein 1, PD-L1 programmed death-ligand 1