Disease Information

General Information of the Disease (ID: DIS00369)

• Name: Lymphatic system cancer
• ICD: ICD-11: 2E81

Type(s) of Resistant Mechanism of This Disease

  ADTT: Aberration of the Drug's Therapeutic Target

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

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

Trametinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: MAPK/ERK kinase 1 (MEK1) [1]

• Sensitive Disease: Lymphatic system cancer [ICD-11: 2E81.1]
• Molecule Alteration: Missense mutation; p.K57N (c.171G>C)
• Sensitive Drug: Trametinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Skin; .
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay

Clinical Trial Drug(s) 1 drug(s) in total

Cobimetinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: MAPK/ERK kinase 1 (MEK1) [2]

• Sensitive Disease: Lymphatic system cancer [ICD-11: 2E81.1]
• Molecule Alteration: Missense mutation; p.P124L (c.371C>T)
• Sensitive Drug: Cobimetinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Whole exome sequencing; Targeted Exon Sequencing
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Key Molecule: MAPK/ERK kinase 1 (MEK1) [1]

• Sensitive Disease: Lymphatic system cancer [ICD-11: 2E81.1]
• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Sensitive Drug: Cobimetinib
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: MAPK/ERK kinase 1 (MEK1) [2]

• Sensitive Disease: Lymphatic system cancer [ICD-11: 2E81.1]
• Molecule Alteration: IF-deletion; p.P105_I107delPAI (c.314_322delCCGCAATCC)
• Sensitive Drug: Cobimetinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Whole exome sequencing; Targeted Exon Sequencing
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Key Molecule: MAPK/ERK kinase 1 (MEK1) [2]

• Sensitive Disease: Lymphatic system cancer [ICD-11: 2E81.1]
• Molecule Alteration: Missense mutation; p.P124Q (c.371C>A)
• Sensitive Drug: Cobimetinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Whole exome sequencing; Targeted Exon Sequencing
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [2]

• Sensitive Disease: Lymphatic system cancer [ICD-11: 2E81.1]
• Molecule Alteration: Complex-indel; p.N486_T491delinsK (c.1458_1472del15)
• Sensitive Drug: Cobimetinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Whole exome sequencing; Targeted Exon Sequencing
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [2]

• Sensitive Disease: Lymphatic system cancer [ICD-11: 2E81.1]
• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Sensitive Drug: Cobimetinib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Whole exome sequencing; Targeted Exon Sequencing
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

References

• Ref 1: Diverse and Targetable Kinase Alterations Drive Histiocytic NeoplasmsCancer Discov. 2016 Feb;6(2):154-65. doi: 10.1158/2159-8290.CD-15-0913. Epub 2015 Nov 13.
• Ref 2: Efficacy of MEK inhibition in patients with histiocytic neoplasmsNature. 2019 Mar;567(7749):521-524. doi: 10.1038/s41586-019-1012-y. Epub 2019 Mar 13.