Table 2.
Summary of preclinical studies with combination treatment for redifferentiation of radioactive-iodine (RAI) refractoriness in differentiated thyroid cancer
| Target | Compound | Type of study | Result | Reference |
|---|---|---|---|---|
| BRAF, HER, MEK | Dabrafenib, Lapatinib, Selumetinib, Lapatinib |
In vitro | NIS, TPO, Tg, TSHR ↑ 125I uptake ↑ 131I cytotoxicity ↑ |
57 |
| BRAF, MEK | Vemurafenib, PD98059 | In vitro | NIS ↑ 125I uptake ↑ |
63 |
| DNA methylation, HDAC | 5-aza-2'-deoxycytidine, Sodium butyrate | In vitro |
NIS ↑ 125I uptake ↑ |
156 |
| 5-aza-2'-deoxycytidine, Valproic acid | In vitro |
NIS ↑ 125I uptake ↑ |
157 | |
| HDAC, MAPK | Vemurafenib, Vorinostat | In vitro | NIS, TPO, Tg, TSHR ↑ 125I uptake ↑ |
19 |
| Selumetinib, Dabrafenib, Panobinostat | In vitro |
NIS, Tg, TSHR, TPO ↑ NIS ↑ 125I uptake ↑ 131I cytotoxicity ↑ |
154 | |
| HDAC, MAPK, PI3K/AKT | RDEA119, Temsirolimus, Perifosine, Vorinostat |
In vitro |
NIS, TSHR, TPO ↑ NIS ↑ 125I uptake ↑ |
16 |
| HDAC, Retinoic acid receptor | Tributyrin, Retinoic acid | In vitro | NIS ↑ 125I uptake ↑ |
155 |
| HMT, MAPK | Dabrafenib, Selumetinib, Tazemetostat | In vitro | NIS, TPO, Tg, TSHR, PAX-8, TTF-1 ↑ 125I uptake ↑ 131I therapy ↑ |
158 |
| MAPK, SAPK/JNK | Sunitinib, Forskolin | In vitro | NIS, TPO, Tg, TSHR, PAX-8 ↑ | 81 |
Abbreviations: HDAC: histone deacetylase; HER: human epidermal growth factor receptor; HMT: histone methyltransferase; MAPK: mitogen-activated protein kinase; NIS: sodium iodide symporter; PAX-8: paired box gene-8; PI3K: phosphoinositide 3-kinase; SAPK/JNK: stress-activated protein kinases/jun amino-terminal kinases; Tg: thyroglobulin; TPO: thyroperoxidase; TSHR: thyroid-stimulating hormone (TSH) receptor; TTF-1: thyroid transcription factor-1.