Molecular Targets and Therapies for Ampullary Cancer

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Monica Arun Patel Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
University of Wisconsin Carbone Cancer Center, Madison, Wisconsin

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Jeremy D. Kratz Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
University of Wisconsin Carbone Cancer Center, Madison, Wisconsin
University of Wisconsin Center for Human Genomics and Precision Medicine, Madison, Wisconsin
William S. Middleton Memorial Veterans Hospital, Shorewood Hills, Wisconsin

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Alexander S. Carlson Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin

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Ysaith Orellana Ascencio Ohio University Heritage College of Osteopathic Medicine, Athens, Ohio

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Broc S. Kelley University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin

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Noelle K. LoConte Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
University of Wisconsin Carbone Cancer Center, Madison, Wisconsin

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Ampullary carcinomas are rare but increasing in incidence. Ampullary cancers have molecular alterations that guide choice of therapy, particularly in nonresectable cases. These alterations can be more common by subtype (intestinal, pancreaticobiliary, or mixed), and next-generation sequencing is recommended for all patients who cannot undergo surgery. In this article, we review the approach to tissue acquisition and consideration for molecular testing. Common molecular targets of interest in ampullary cancer are also discussed in this review, including HER2/ERBB2, HER3, tumor mutational burden, microsatellite instability, KRAS, and germline BRCA and ATM mutations, along with emerging and rarer alterations.

Submitted March 30, 2023; final revision received June 20, 2023; accepted for publication June 22, 2023. Published online January 5, 2024.

M.A. Patel and J.D. Kratz are co–first authors.

Disclosures: Dr. LoConte has disclosed serving as a scientific advisor for PDGx and AbbVie. The remaining authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.

Funding: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award number P30 CA014520.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Correspondence: Noelle LoConte, MD, University of Wisconsin Carbone Cancer Center, 600 Highland Avenue, MC 5666, Madison, WI 53792. Email: ns3@medicine.wisc.edu
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