Drug Information

Drug (ID: DG00418) and It's Reported Resistant Information

• Name: Iodine-131
• Synonyms: IODINE-131; Iodine 131; UNII-I5X6L61HUT; I5X6L61HUT; 10043-66-0; I-131; Iodine I 131; Radioactive iodine-I131; Radioactive iodine (131I); Iodine, mol. (131I2); Iodine, isotope of mass 131; Iodine, labeled with iodine-131; I 131; 15124-39-7
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Thyroid cancer [ICD-11: 2D10]; [1]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Thyroid cancer [ICD-11: 2D10]; [2]
• Formula: I2
• IsoSMILES: [131I][131I]
• InChI: 1S/I2/c1-2/i1+4,2+4
• InChIKey: PNDPGZBMCMUPRI-HVTJNCQCSA-N
• PubChem CID: 24855

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Thyroid cancer [ICD-11: 2D10]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Solute carrier family 6 member 9 (SLC6A9) [3]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Papillary thyroid carcinoma [ICD-11: 2D10.1]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: SLC6A9/PARP1 signaling pathway; Inhibition; hsa04064
• In Vitro Model: BCPAP cells; Thyroid; Homo sapiens (Human); CVCL_0153
• In Vitro Model: TPC-1 cells; Thyroid; Homo sapiens (Human); CVCL_6298
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: SLC6A9-5:2 overexpression was positively correlated with PARP-1 mRNA and protein levels, which restored the sensitivity of resistant thyroid cancer cells. SLC6A9 is positively correlated with PARP-1 expression, and PARP-1 inhibition makes thyroid cancer cells resistant to 131I. Upregulation of the SLC6A9-PARP-1 pathway enhanced the sensitivity to 131I treatment through energy exhaustion during excess RNA repair.

Key Molecule: hsa-mir-182 [2]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Thyroid carcinoma [ICD-11: 2D10.4]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: TPC-1 cells; Thyroid; Homo sapiens (Human); CVCL_6298
• In Vitro Model: FTC-133 cells; Thyroid; Homo sapiens (Human); CVCL_1219
• Experiment for Molecule Alteration: qRT-PCR; Luciferase reporter assay
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: MEG3 expression was decreased while miR-182 expression was increased in 131I-resistant TC cells.

Key Molecule: Maternally expressed 3 (MEG3) [2]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Thyroid carcinoma [ICD-11: 2D10.4]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: TPC-1 cells; Thyroid; Homo sapiens (Human); CVCL_6298
• In Vitro Model: FTC-133 cells; Thyroid; Homo sapiens (Human); CVCL_1219
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: MEG3 expression was decreased while miR-182 expression was increased in 131I-resistant TC cells.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Poly[ADP-ribose] synthase 1 (PARP1) [3]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Papillary thyroid carcinoma [ICD-11: 2D10.1]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: SLC6A9/PARP1 signaling pathway; Inhibition; hsa04064
• In Vitro Model: BCPAP cells; Thyroid; Homo sapiens (Human); CVCL_0153
• In Vitro Model: TPC-1 cells; Thyroid; Homo sapiens (Human); CVCL_6298
• Experiment for Molecule Alteration: Western blot analysis; qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: SLC6A9-5:2 overexpression was positively correlated with PARP-1 mRNA and protein levels, which restored the sensitivity of resistant thyroid cancer cells. SLC6A9 is positively correlated with PARP-1 expression, and PARP-1 inhibition makes thyroid cancer cells resistant to 131I. Upregulation of the SLC6A9-PARP-1 pathway enhanced the sensitivity to 131I treatment through energy exhaustion during excess RNA repair.

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [1]

• Molecule Alteration: Missense mutation; p.V600E
• Resistant Disease: Thyroid carcinoma [ICD-11: 2D10.4]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: Epigenetic signaling pathway; Activation; hsa05207
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Low throughput experiment assay
• Mechanism Description: Primary resistance appears to develop early in tumorigenesis via genetic or epigenetic events that activate pro-proliferation pathways or inhibit pathways that stimulate cell death. Loss or gain of a cell surface receptor or transporter or other alterations in the drug target pathway can also lead to resistance against pharmacological agents, as described below for PTC with the BRAFV600E mutation. BRA FV600E PTC exhibits primary resistance to RAI treatment, higher rates of tumor recurrence and metastases, and lower survival rates. Remarkably, the BRAFV600E mutation not only promotes thyroid tumor cell proliferation, adhesion, migration and invasion, but also up-regulates epigenetic pathways that silence expression of the sodium/iodide symporter. This blocks iodide uptake, which may be one cause of primary resistance to RAI. BRAF V600E PTC exhibits primary resistance to RAI treatment, higher rates of tumor recurrence and metastases, and lower survival rates.

References

• Ref 1: Evolution of resistance to thyroid cancer therapy. Aging (Albany NY). 2016 Aug;8(8):1576-7. doi: 10.18632/aging.101030.
• Ref 2: LncRNA MEG3 enhances (131)I sensitivity in thyroid carcinoma via sponging miR-182. Biomed Pharmacother. 2018 Sep;105:1232-1239. doi: 10.1016/j.biopha.2018.06.087. Epub 2018 Jun 22.
• Ref 3: LncRNA-SLC6A9-5:2: A potent sensitizer in 131I-resistant papillary thyroid carcinoma with PARP-1 induction. Oncotarget. 2017 Apr 4;8(14):22954-22967. doi: 10.18632/oncotarget.14578.