Reference Detail

Ref Type Journal Article
PMID (26633560)
Authors Amatu A, Somaschini A, Cerea G, Bosotti R, Valtorta E, Buonandi P, Marrapese G, Veronese S, Luo D, Hornby Z, Multani P, Murphy D, Shoemaker R, Lauricella C, Giannetta L, Maiolani M, Vanzulli A, Ardini E, Galvani A, Isacchi A, Sartore-Bianchi A, Siena S
Title Novel CAD-ALK gene rearrangement is drugable by entrectinib in colorectal cancer.
Journal British journal of cancer
Vol 113
Issue 12
Date 2015 Dec 22
Abstract Text Activated anaplastic lymphoma kinase (ALK) gene fusions are recurrent events in a small fraction of colorectal cancers (CRCs), although these events have not yet been exploited as in other malignancies.We detected ALK protein expression by immunohistochemistry and gene rearrangements by fluorescence in situ hybridisation in the ALKA-372-001 phase I study of the pan-Trk, ROS1, and ALK inhibitor entrectinib. One out of 487 CRCs showed ALK positivity with a peculiar pattern that prompted further characterisation by targeted sequencing using anchored multiplex PCR.A novel ALK fusion with the carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD) gene (CAD-ALK fusion gene) was identified. It resulted from inversion within chromosome 2 and the fusion of exons 1-35 of CAD with exons 20-29 of ALK. After failure of previous standard therapies, treatment of this patient with the ALK inhibitor entrectinib resulted in a durable objective tumour response.We describe the novel CAD-ALK rearrangement as an oncogene and provide the first evidence of its drugability as a new molecular target in CRC.


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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
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
ALK fusion colorectal cancer sensitive Entrectinib Phase I Actionable In a Phase I clinical trial, Entrectinib (RXDX-101) treatment resulted in partial response for more than 3 months in a colorectal cancer patient harboring a CAD-ALK gene fusion (PMID: 26633560). 26633560