Background
Clinical manifestation and diagnosis
Current therapeutic regimes
Surgical resection
External beam radiation therapy
Chemotherapy
Targeted/multi-targeted inhibitors
No. | Drug | Phase | Cancer | Number of patients | Response Rate | Progression free survival | Overall survival | Reference |
---|---|---|---|---|---|---|---|---|
1 | Sorafenib (Bay43–9006, Nexavar) | II | ATC | 20 | PR in 2/20 (10%); Stable disease in 5/20 (25%) | 1.9 months | – | [107] |
2 | Carbozantinib | III | MTC | 330 | 28% | 11.2 | – | [108] |
3 | Efatutazone+ Paclitaxel | I | ATC | 15 | PR = 1; SD = 7 | 3.3 months | – | [39] |
4 | Pazopanib | II | Advanced and progressive medullary | 35 | 5/35 | 9.4 | 19.9 | [109] |
5 | Fosbretabulin + Paclitaxel/Carboplatin | II | ATC | 8 | 20% | 3.3 | 5.2 months | [110] |
6 | Vemurafenib | BRAFV600E positive, metastatic, radio-iodine refractory PTC | 26 | 10/26 | – | – | [110] | |
7 | Axitinib | II | Advanced thyroid cancer | 52 | 35% | 16.1 | 23.2 | [111] |
8 | Levatinib | III | Iodine refractor TC | 261 | 64.8% | 18.3 | – | [112] |
9 | Sunitinib (second line of therapy) | II | Progressive, radio-iodine Refractory thyroid cancer | 25 | 5/20 (25%) | 6 months | 13 months | [113] |
10 | Cabozantinib (XL-184) | III | Advanced MTC | 11.2 months | – | [114] | ||
11 | Dabrafenib plus trametinib | II | BRAF V600E–mutated anaplastic thyroid cancer | 16 | 69% | – | – | [23] |
Ongoing clinical trials
S. No | Phase | Drug | Drug Action | Clinical Trial No. | Status | Sponsors |
---|---|---|---|---|---|---|
1 | II | MLN0128 | mTOR kinase inhibitor | NCT02244463 | Recruiting | Dana-Farber Cancer Institute, USA |
2 | II | Lenvatinib | MKI against VEGFR1, 2, and 3 | NCT02726503 | Recruiting | Translational Research Informatics Center, Kobe, Hyogo, Japan |
NCT02657369 | Recruiting | Eisai Inc. USA | ||||
3 | Early phase I | Trametinib in combination with Paclitaxel | MEK inhibitor (Trametinib) with chemotherapy | NCT03085056 | Recruiting | Memorial Sloan Kettering Cancer Center, USA |
4 | II | Pembrolizumab | Antibody against PD-1 receptor | NCT02688608 | Recruiting | University of Texas Southwestern Medical Center, USA |
5 | II | Inolitazone Dihydrochloride (Efutazone) and Paclitaxel | PPAR-γ agonist (Efutazone) with chemotherapy | NCT02152137 | Recruiting | Alliance for Clinical Trials in Oncology, USA |
6 | I | Combination of Durvalumab (MEDI4736) or Tremelimumab with Stereotactic Body Radiotherapy (SBRT) | Checkpoint inhibitor drugs: Durvalumab (PD-1/PDL-1 interaction blocker) and Tramelimumab (anti-CTLA4 antibody) with radiations | NCT03122496 | Recruiting | Memorial Sloan Kettering Cancer Center, USA |
7 | II | Intensity-Modulated Radiation Therapy and Paclitaxel with or Without Pazopanib Hydrochloride | Pazopanib is a MKI against c-kit, FGFR, PDGFR and VEGFR | NCT01236547 | Ongoing but not yet recruiting participants | National Cancer Institute (NCI), USA |
8. | II | Ceritinib | ALK inhibitor | NCT02289144 | Recruiting | University of Texas Southwestern Medical Center, USA |
9 | II | Atezolizumab Combinations with or without chemotherapy such as paclitaxel, Vemurifinib, Nab-paclitaxel, Cobimetinib and Bevacizumab | anti-PDL-1 antibody (Atezolizumab) | NCT03181100 | Recruiting | M.D. Anderson Cancer Center, USA |
10 | I | FAZ053 as Single Agent and in combination with PDR001 | FAZ053 is anti-PDL-1 antibody and PDR001 is monoclonal antibody against PD-1. | NCT02936102 | Recruiting | Novartis Pharmaceuticals, USA |
11 | II | Dabrafenib and Trametinib | Dabrafenib acts against BRAFV600E mutations and Trametinib is MEK (1 and 2) inhibitor | NCT02034110 | Recruiting | GlaxoSmithKline, USA |
12 | II | GW 786034 (Pazopanib Hydrochloride) | Pazopanib is a MKI against c-kit, FGFR, PDGFR and VEGFR | NCT00625846 | Active, not recruiting | National Cancer Institute (NCI), USA |
13 | II | Pembrolizumab, Chemotherapy,and Radiation Therapy With or Without Surgery | anti-PD1 immunotherapy | NCT03211117 | Active, not recruiting | Mayo Clinic,National Cancer Institute (NCI), USA |
14 | I/II | PDR001 | anti-PD1 monoclonal antibody | NCT02404441 | Recruiting | Novartis Pharmaceuticals |
Promising therapeutic options
Aurora kinase inhibitors
Natural/synthetic compounds
Gene therapy using oncolytic viruses
Novel targeted inhibitors
Chemotherapeutic agents | |
---|---|
Topoisomerase inhibitor | Doxorubicin, Etoposide |
Microtubule assembly | Paclitaxel, Vinorelbine, Docetaxel |
DNA crosslinking agents | Cisplatin, Carboplatin, Cyclophosphamide, Neoplatin |
Nucleoside Analog | Gemcitabine, 5- fluorouracil |
Targeted inhibitors/antibodies | |
ALK1 | GSK461364A |
Akt | MK-2206 2HCL, Perifosine, GSK690693, GDC-0068, AT7867 |
Aurora Kinases | MK-0457 (VX-680), SNS-314 mesylate, ZM447439, AZD1152 and MLN8054 |
Bcl2 | Obatoclax |
CDK | BP14 |
EGFR | Cetuximab (C225), Manumycin A, Geldanamycin, Gefitinib (ZD1839) |
HSP90 | Tanespimycin (17-N-allylamino-17-demethoxygeldanamycin, NVP-A0Y922, SNX5422 |
I-κB | Ciglitazone (upregulates TrailR1, −R2) |
PARP | Olaparib |
PD-1 receptor | Pembrolizumab, PDR001 |
PDL-1 | Durvalumab, Atezolizumab, FAZ053 |
CTLA4 | Tramelimumab |
TGF-β | LY2157299, SB 525334, LY2109761, Perfenidone, GW788388 |
SMO (Wnt signaling pathway) | LDE225, LY2940680, PF-5274857, SANT-1 |
γ-secretase | RO4929097, LY-411575 |
Anti-angiogenic agents | |
Vascular disrupting agent | Combretastatin A4 phosphate (CA4P), Fosbretabulin |
VEGF | Bevacizumab, AZD2171, Cediranib |
Multi-Kinase inhibitors | |
VEGF 1, 2 and 3, PDGFR and c-KIT | Axitinib (AG-013736), Pazopanib |
VEGFR1, 2 and 3, EGFR and RET kinases | Vandetanib |
VEGFR-1, PDGFR, RET, FLT-3 and CSF-1R | Sunitinib |
VEGFR2, EGFR and RET | CLM94 |
BCR-ABL, PDGFR and c-kit | Imatinib |
VEGFR 1, 2, PDGFRβ, RET, BRAF and c-Kit | Sorafenib (Bay43–9006, Nexavar) |
VEGFR-1, −2 and − 3, PDGFRβ, RET, FGFR −1, − 2, −3, −4 and c-KIT | Lenvatinib (E7080) |
VEGFR 2, RET, MET, kit | Cabozantinib |
VEGFR −1, − 2, −3, RET, kit, PDGFR | Motesanib |
VEGFR − 1, −3, PDGFR, FGFR1–3 | Ninetedanib |
RET, PDGFR, FGFR, FLT3, kit | Ponatinib |
MET, ALK, ROS1 | Crizotinib |
Epigenetic modifiers | |
HDAC inhibitors | Valproic acid, Thailandepsin A (TDP-A), Trichostatin A (TSA), Suberoyl Amide Hydroxamic Acid (SAHA), N-hydroxy-7-(2-naphthylthio)heptanomide (HNHA) |
BET inhibitors | JQ1, I-BET762 |
Miscellaneous | |
HDACs, EGFR (dual inhibitor) | CUDC-101 |
Proteosome inhibitors | Carfilzomib, Bortezomib (PS-341) |
PPARγ agonists | Rosiglitazone, RS5444, Pioglitazone, Troglitazone |