TABLE 1.
| Endogenous Differentiated Thyroid Cancer-Specific Signaling Pathways | |||||
| Pathway | Histotypes | Cellular Effects | Therapeutic approach | ||
| Sodium iodide symporter (NIS) | DTC | ↑ Proliferation | Radioiodine | ||
| Thyrotropin/Thyroid Stimulating Hormone (TSH) | DTC | ↑ Proliferation | Suppressive dosage levothyroxine | ||
| Mutations in Thyroid Cancers | |||||
| Pathway | Activating/Inactivating | Histotypes | Prevalence | Cellular Effects | Targeted agents |
| RET, RET/PTC | Activating | MTC PTC |
>60% 25% |
↑Proliferation | Vandetanib |
| BRAFV600E | Activating | PTC ATC |
45% 26% |
↑ Proliferation | AZD6244, GSK1120212, GSK2118436 |
| PAX8/PPARγ | Disputed (activating or inactivating) | FTC | 45% | (complex) | Rosiglitazone. RS5444 |
| P53 | Inactivating | ATC | 55–70% | ↑ Proliferation | rAd-p53 |
| RAS | Activating | PTC FTC ATC |
10% 45% 22–55% |
↑ Proliferation | |
| PTEN | Inactivating | ATC | 12% | ↑ Proliferation | |
| EGF-R | Activating | PTC MTC ATC |
15% 35% (mets) 80% |
↑ Proliferation | Cetuximab, erlotinib, gefitinib, panitumumab |
| PI3K | Activating | ATC | 17% | ↑ Proliferation | NVP-BEZ235 |
| Axin-1 | Inactivating | ATC | 82% | ↑ Proliferation | |
| APC | Inactivating | ATC | 9% | ↑ Proliferation | |
| Additional Altered Signaling Pathways in Thyroid Cancers | |||||
| Pathway | Alteration | Histotypes | Cellular Effects | Targeted agents | |
| VEGF/VEGF-R | Up | PTC, FTC, MTC, ATC | ↑ Proliferation | Sunitinib, sorafenib, pazopanib | |
| mTOR | Up | ↑ Proliferation | Everolimus, Temsirolimus | ||
| β-Catenin | Up | ATC | ↑ Proliferation | ||
| Aurora A, B | Up | ATC | ↑ Proliferation | MLN8237 | |
| RAR, RXR | PTC, FTC | ↑ Proliferation | Acitretin, Bexarotene, retinoic acid | ||
| Somatostatin | Up | MTC, PTC | ↓ Proliferation | Octreotide/Lanreotide and radiotherapeutic conjugates | |
| IGF-R | Up | ↑ Proliferation | AG38A, AG1024, figitumumab, NVP-AEW541 | ||