Disease Information

General Information of the Disease (ID: DIS00087)

• Name: Breast lactating adenoma
• ICD: ICD-11: 2F30

Type(s) of Resistant Mechanism of This Disease

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

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

Entrectinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: NT-3 growth factor receptor (TrkC) [1]

• Resistant Disease: Mammary analogue secretory carcinoma [ICD-11: 2F30.1]
• Molecule Alteration: Missense mutation; p.G623R
• Resistant Drug: Entrectinib
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Whole genome sequencing assay
• Mechanism Description: A dramatic and durable response was achieved with entrectinib in this patient, followed by acquired resistance that correlated with the appearance of a novel NTRK3 G623R mutation. Investigation into the structural impact of the G623R point mutation revealed a potential mechanism of relative resistance to entrectinib and other Trk inhibitors. The NTRK3 G623R mutation creates steric hindrance that functionally reduces the binding of entrectinib with mutant TrkC.

References

• Ref 1: What hides behind the MASC: clinical response and acquired resistance to entrectinib after ETV6-NTRK3 identification in a mammary analogue secretory carcinoma (MASC) .Ann Oncol. 2016 May;27(5):920-6. doi: 10.1093/annonc/mdw042. Epub 2016 Feb 15. 10.1093/annonc/mdw042