Drug Information

Drug (ID: DG00471) and It's Reported Resistant Information

• Name: Exemestane/Everolimus
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (2 diseases)
  Breast cancer [ICD-11: 2C60]; [1]
  COVID-19 [ICD-11: 1D92]; [2]

Type(s) of Resistant Mechanism of This Drug

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Breast cancer [ICD-11: 2C60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Estrogen receptor alpha (ESR1) [1]

• Molecule Alteration: Missense mutation; p.Y537S
• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Next-generation sequencing assay
• Experiment for Drug Resistance: Overall survival assay
• Mechanism Description: All 28 patients were found to harbor ESR1 mutations affecting ligand-binding domain with the most common mutations affecting Y537 (17/28, 60.7%) and D538 (9/28, 32.1%). ESR1 mutation was found in 12.1% of a large cohort of advanced breast cancer patients. Exemestane in combination with everolimus might be a reasonable option. Prospective studies are warranted to validate these findings.

Key Molecule: Estrogen receptor alpha (ESR1) [1]

• Molecule Alteration: Missense mutation; p.L536_D538>P
• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Next-generation sequencing assay
• Experiment for Drug Resistance: Overall survival assay
• Mechanism Description: All 28 patients were found to harbor ESR1 mutations affecting ligand-binding domain with the most common mutations affecting Y537 (17/28, 60.7%) and D538 (9/28, 32.1%). ESR1 mutation was found in 12.1% of a large cohort of advanced breast cancer patients. Exemestane in combination with everolimus might be a reasonable option. Prospective studies are warranted to validate these findings.

Key Molecule: Estrogen receptor alpha (ESR1) [1]

• Molecule Alteration: Missense mutation; p.D538G
• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Next-generation sequencing assay
• Experiment for Drug Resistance: Overall survival assay
• Mechanism Description: All 28 patients were found to harbor ESR1 mutations affecting ligand-binding domain with the most common mutations affecting Y537 (17/28, 60.7%) and D538 (9/28, 32.1%). ESR1 mutation was found in 12.1% of a large cohort of advanced breast cancer patients. Exemestane in combination with everolimus might be a reasonable option. Prospective studies are warranted to validate these findings.

References

• Ref 1: Incidence and clinical significance of ESR1 mutations in heavily pretreated metastatic breast cancer patients. Onco Targets Ther. 2015 Nov 11;8:3323-8. doi: 10.2147/OTT.S92443. eCollection 2015.
• Ref 2: Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies Nat Med. 2021 Apr;27(4):717-726. doi: 10.1038/s41591-021-01294-w. Epub 2021 Mar 4.