Reference Detail

Ref Type

Journal Article

PMID

(18606718)

Authors

Gonzales AJ, Hook KE, Althaus IW, Ellis PA, Trachet E, Delaney AM, Harvey PJ, Ellis TA, Amato DM, Nelson JM, Fry DW, Zhu T, Loi CM, Fakhoury SA, Schlosser KM, Sexton KE, Winters RT, Reed JE, Bridges AJ, Lettiere DJ, Baker DA, Yang J, Lee HT, Tecle H, Vincent PW

Title

Antitumor activity and pharmacokinetic properties of PF-00299804, a second-generation irreversible pan-erbB receptor tyrosine kinase inhibitor.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Molecular cancer therapeutics	7	7	2008 Jul	1880-9	Mol Cancer Ther

URL

Abstract Text

Signaling through the erbB receptor family of tyrosine kinases contributes to the proliferation, differentiation, migration, and survival of a variety of cell types. Abnormalities in members of this receptor family have been shown to play a role in oncogenesis, thus making them attractive targets for anticancer treatments. PF-00299804 is a second-generation irreversible pan-erbB receptor tyrosine kinase inhibitor currently in phase I clinical trials. PF-00299804 is believed to irreversibly inhibit erbB tyrosine kinase activity through binding at the ATP site and covalent modification of nucleophilic cysteine residues in the catalytic domains of erbB family members. Oral administration of PF-00299804 causes significant antitumor activity, including marked tumor regressions in a variety of human tumor xenograft models that express and/or overexpress erbB family members or contain the double mutation (L858R/T790M) in erbB1 (EGFR) associated with resistance to gefitinib and erlotinib. Furthermore, PF-00299804 shows exceptional distribution to human tumor xenografts and excellent pharmacokinetic properties across species.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
Dacomitinib	Dacomitinib	0	8
Dacomitinib + Osimertinib	Dacomitinib Osimertinib	0	1

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
Dacomitinib	Vizimpro	PF-00299804\|PF299804	EGFR Inhibitor 2nd gen 5 HER inhibitor (Pan) 6	Vizimpro (dacomitinib) is a second-generation EGFR inhibitor and pan-HER inhibitor that inhibits HER2 and multiple EGFR subtypes including EGFR T790M, resulting in decreased proliferation and increased apoptosis in EGFR-expressing and HER2-expressing tumor cells (PMID: 22761403, PMID: 18606718). Vizimpro (dacomitinib) is FDA approved for use in patients with metastatic non-small cell lung cancer with EGFR exon 19 deletion or L858R mutation as first-line treatment (FDA.gov).

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References