Disease Information

General Information of the Disease (ID: DIS00203)

• Name: Chordoma
• ICD: ICD-11: 2B5J

Type(s) of Resistant Mechanism of This Disease

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 3 drug(s) in total

Afatinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Y-box-binding protein 1 (YBX1) [1]

• Resistant Disease: Chordoma [ICD-11: 2B5J.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Afatinib
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR/AKT signaling pathway; Regulation; hsa04012
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• In Vitro Model: Chordoma tissue; .
• In Vivo Model: NOD/SCID/IL2Rgamma null (NOG) mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: YBX1 regulated protein expression of pEGFR, pAKT and its downstream target genes that influenced cell apoptosis, cell cycle transition and cell invasion. YBX1 activated the EGFR/AKT pathway in chordoma and YBX1-induced elevated expression of key molecules in the EGFR/AKT pathway were downregulated by EGFR and AKT pathway inhibitors. These in vitro results were further confirmed by in vivo data. These data showed that YBX1 promoted tumorigenesis and progression in spinal chordoma via the EGFR/AKT pathway. YBX1 might serve as a prognostic and predictive biomarker, as well as a rational therapeutic target, for chordoma.

Erlotinib HCI

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Y-box-binding protein 1 (YBX1) [1]

• Resistant Disease: Chordoma [ICD-11: 2B5J.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Erlotinib HCI
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR/AKT signaling pathway; Regulation; hsa04012
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• In Vitro Model: Chordoma tissue; .
• In Vivo Model: NOD/SCID/IL2Rgamma null (NOG) mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: YBX1 regulated protein expression of pEGFR, pAKT and its downstream target genes that influenced cell apoptosis, cell cycle transition and cell invasion. YBX1 activated the EGFR/AKT pathway in chordoma and YBX1-induced elevated expression of key molecules in the EGFR/AKT pathway were downregulated by EGFR and AKT pathway inhibitors. These in vitro results were further confirmed by in vivo data. These data showed that YBX1 promoted tumorigenesis and progression in spinal chordoma via the EGFR/AKT pathway. YBX1 might serve as a prognostic and predictive biomarker, as well as a rational therapeutic target, for chordoma.

Sirolimus

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Y-box-binding protein 1 (YBX1) [1]

• Resistant Disease: Chordoma [ICD-11: 2B5J.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Sirolimus
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR/AKT signaling pathway; Regulation; hsa04012
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• In Vitro Model: Chordoma tissue; .
• In Vivo Model: NOD/SCID/IL2Rgamma null (NOG) mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: YBX1 regulated protein expression of pEGFR, pAKT and its downstream target genes that influenced cell apoptosis, cell cycle transition and cell invasion. YBX1 activated the EGFR/AKT pathway in chordoma and YBX1-induced elevated expression of key molecules in the EGFR/AKT pathway were downregulated by EGFR and AKT pathway inhibitors. These in vitro results were further confirmed by in vivo data. These data showed that YBX1 promoted tumorigenesis and progression in spinal chordoma via the EGFR/AKT pathway. YBX1 might serve as a prognostic and predictive biomarker, as well as a rational therapeutic target, for chordoma.

Investigative Drug(s) 1 drug(s) in total

PKI-587

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Y-box-binding protein 1 (YBX1) [1]

• Resistant Disease: Chordoma [ICD-11: 2B5J.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: PKI-587
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR/AKT signaling pathway; Regulation; hsa04012
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• In Vitro Model: Chordoma tissue; .
• In Vivo Model: NOD/SCID/IL2Rgamma null (NOG) mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: YBX1 regulated protein expression of pEGFR, pAKT and its downstream target genes that influenced cell apoptosis, cell cycle transition and cell invasion. YBX1 activated the EGFR/AKT pathway in chordoma and YBX1-induced elevated expression of key molecules in the EGFR/AKT pathway were downregulated by EGFR and AKT pathway inhibitors. These in vitro results were further confirmed by in vivo data. These data showed that YBX1 promoted tumorigenesis and progression in spinal chordoma via the EGFR/AKT pathway. YBX1 might serve as a prognostic and predictive biomarker, as well as a rational therapeutic target, for chordoma.

References

• Ref 1: Y-box binding protein-1 promotes tumorigenesis and progression via the epidermal growth factor receptor/AKT pathway in spinal chordoma .Cancer Sci. 2019 Jan;110(1):166-179. doi: 10.1111/cas.13875. Epub 2018 Dec 19. 10.1111/cas.13875