Drug Information

Drug (ID: DG01721) and It's Reported Resistant Information

• Name: Dactolisib/Selumetinib
• Synonyms: Dactolisib/Selumetinib
• Target: .; NOUNIPROTAC; [1]

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

Colorectal cancer [ICD-11: 2B91]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: GTPase KRas (KRAS) [1]

• Molecule Alteration: Missense mutation; p.A146T (c.436G>A)
• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Liver; N.A.
• In Vivo Model: Female nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunohistochemistry assay
• Mechanism Description: The missense mutation p.A146T (c.436G>A) in gene KRAS cause the sensitivity of Dactolisib + Selumetinib by unusual activation of pro-survival pathway

Key Molecule: GTPase KRas (KRAS) [1]

• Molecule Alteration: Missense mutation; p.G13D (c.38G>A)
• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Liver; N.A.
• In Vivo Model: Female nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunohistochemistry assay
• Mechanism Description: The missense mutation p.G13D (c.38G>A) in gene KRAS cause the sensitivity of Dactolisib + Selumetinib by unusual activation of pro-survival pathway

Lung cancer [ICD-11: 2C25]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: GTPase KRas (KRAS) [2]

• Molecule Alteration: Missense mutation; p.G12D (c.35G>A)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Mechanism Description: The missense mutation p.G12D (c.35G>A) in gene KRAS cause the sensitivity of Dactolisib + Selumetinib by unusual activation of pro-survival pathway

References

• Ref 1: Inhibition of MEK and PI3K/mTOR suppresses tumor growth but does not cause tumor regression in patient-derived xenografts of RAS-mutant colorectal carcinomasClin Cancer Res. 2012 May 1;18(9):2515-25. doi: 10.1158/1078-0432.CCR-11-2683. Epub 2012 Mar 5.
• Ref 2: Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancersNat Med. 2008 Dec;14(12):1351-6. doi: 10.1038/nm.1890. Epub 2008 Nov 30.