Reference Detail

Ref Type

PMID

Authors

James M. Cleary, Srivatsan Raghavan, Yvonne Y. Li, Liam Spurr, Qibiao Wu, Lei Shi, Lauren K. Brais, Zunelly Odhiambo, Lipika Goyal, Anuj K. Patel, Atul B. Shinagare, Thomas E. Clancy, Geoffrey Shapiro, Ethan Cerami, William R. Sellers, William C. Hahn, Andrew D. Cherniack, Nabeel Bardeesy, Matthew Meyerson, Brian M. Wolpin

Title

Therapeutic targeting of extracellular FGFR2 activating deletions in intrahepatic cholangiocarcinoma.

Journal	Vol	Issue	Date	Pages	Journal Short Title

URL

https://meetinglibrary.asco.org/record/182230/abstract

Abstract Text

J Clin Oncol 38, 2020 (suppl 4; abstr 567)

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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

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance
FGFR2	H167_N173del	deletion	gain of function	FGFR2 H167_N173del results in the deletion of seven amino acids in Ig-like C2-type domain 2 of the Fgfr2 protein from amino acids 167 to 173 (UniProt.org). H167_N173del results in cell transformation (J Clin Oncol 38, 2020 (suppl 4; abstr 567), PMID: 33926920), increased proliferation, invasion, and migration (PMID: 37964396), anchorage-independent growth, constitutive activation of Fgfr2 kinase activity in culture, and tumor formation in an in vivo model (PMID: 33926920).

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
FGFR2 H167_N173del	intrahepatic cholangiocarcinoma	predicted - sensitive	Zoligratinib	Case Reports/Case Series	Actionable	In a clinical study, Debio 1347 treatment resulted in durable partial response of 11 months in 2 patients with intrahepatic cholangiocarcinoma harboring FGFR2 H167_N173del (J Clin Oncol 38, 2020 (suppl 4; abstr 567)).	detail...
FGFR2 H167_N173del FGFR2 L617F	intrahepatic cholangiocarcinoma	predicted - resistant	Zoligratinib	Case Reports/Case Series	Actionable	In a clinical study, a patient with intrahepatic cholangiocarcinoma harboring FGFR2 H167_N173del developed resistance to Debio 1347 treatment after initial response, FGFR2 L617F was identified as an acquired mutation at disease progression (J Clin Oncol 38, 2020 (suppl 4; abstr 567)).	detail...