Disease Information

General Information of the Disease (ID: DIS00214)

• Name: Neuroendocrine carcinoma
• ICD: ICD-11: 2D4Y

Type(s) of Resistant Mechanism of This Disease

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Dabrafenib/Trametinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

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

• Sensitive Disease: Metastatic neuroendocrine carcinoma [ICD-11: 2D4Y.0]
• Molecule Alteration: Missense mutation; p.V600E (c.1406G>C)
• Sensitive Drug: Dabrafenib/Trametinib
• Experimental Note: Identified from the Human Clinical Data

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

• Sensitive Disease: Metastatic neuroendocrine carcinoma [ICD-11: 2D4Y.0]
• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Sensitive Drug: Dabrafenib/Trametinib
• Experimental Note: Identified from the Human Clinical Data

Nivolumab

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [2]

• Resistant Disease: Primary pulmonary lymphoepithelioma-like carcinoma [ICD-11: 2D4Y.Z]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Nivolumab
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: KB-3-1 cells; Lung; Homo sapiens (Human); CVCL_2088
• Mechanism Description: Pulmonary LELC with FGFR3 gene amplification may not respond well to nivolumab monotherapy. The combination of anlotinib and nivolumab can reverse the resistance to nivolumab in pulmonary LELC with FGFR3 gene amplification.

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

Trametinib/Vemurafenib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

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

• Sensitive Disease: Metastatic neuroendocrine carcinoma [ICD-11: 2D4Y.0]
• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Sensitive Drug: Trametinib/Vemurafenib
• Experimental Note: Identified from the Human Clinical Data

References

• Ref 1: BRAFV600E Mutations in High-Grade Colorectal Neuroendocrine Tumors May Predict Responsiveness to BRAF-MEK Combination TherapyCancer Discov. 2016 Jun;6(6):594-600. doi: 10.1158/2159-8290.CD-15-1192. Epub 2016 Apr 5.
• Ref 2: Case Report: Anlotinib Reverses Nivolumab Resistance in Advanced Primary Pulmonary Lymphoepithelioma-Like Carcinoma With FGFR3 Gene Amplification .Front Oncol. 2021 Oct 8;11:749682. doi: 10.3389/fonc.2021.749682. eCollection 2021. 10.3389/fonc.2021.749682