Drug Information

Drug (ID: DG01748) and It's Reported Resistant Information

• Name: Palbociclib/PD-0325901
• Synonyms: Palbociclib/PD-0325901
• 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

Melanoma [ICD-11: 2C30]

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]

• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: CDK4/6 signaling pathway; Regulation; hsa04218
• Cell Pathway Regulation: MEK signaling pathway; Inhibition; hsa04011
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: WM cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: SKMEL207 cells; Skin; Homo sapiens (Human); CVCL_6108
• In Vitro Model: SBCL2 cells; Skin; Homo sapiens (Human); CVCL_D732
• In Vitro Model: CHL-1 cells; Pleural effusion; Homo sapiens (Human); CVCL_1122
• In Vitro Model: BOWES cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: 1205Lu cells; Skin; Homo sapiens (Human); CVCL_5239
• In Vivo Model: Female athymic mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay; Crystal violet staining assay
• Mechanism Description: In cutaneous melanoma, driver mutations in NRAS and BRAF promote CDK4/6 activation suggesting that inhibitors such as palbociclib are likely to provide therapeutic benefit in combination with BRAF inhibitors and/or MEK inhibitors that are FDA-approved. However, the determinants of the response to CDK4/6 inhibitors alone and in combination with other targeted inhibitors are poorly defined. Furthermore, in vivo systems to quantitatively and temporally measure the efficacy of CDK4/6 inhibitors and determine the extent that CDK activity is reactivated during acquired resistance are lacking.

References

• Ref 1: An In Vivo Reporter to Quantitatively and Temporally Analyze the Effects of CDK4/6 Inhibitor-Based Therapies in MelanomaCancer Res. 2016 Sep 15;76(18):5455-66. doi: 10.1158/0008-5472.CAN-15-3384. Epub 2016 Aug 3.