Genomics driven precision oncology in advanced biliary tract cancer improves survival.

Autor:	Kumar-Sinha C; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA., Vats P; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA., Tran N; Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA., Robinson DR; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA., Gunchick V; Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA., Wu YM; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA., Cao X; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA., Ning Y; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA., Wang R; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA., Rabban E; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA., Bell J; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA., Shankar S; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA., Mannan R; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA., Zhang Y; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA., Zalupski MM; Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA., Chinnaiyan AM; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: arul@umich.edu., Sahai V; Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: vsahai@umich.edu.
Jazyk:	angličtina
Zdroj:	Neoplasia (New York, N.Y.) [Neoplasia] 2023 Aug; Vol. 42, pp. 100910. Date of Electronic Publication: 2023 May 31.
DOI:	10.1016/j.neo.2023.100910
Abstrakt:	Background: Biliary tract cancers (BTCs) including intrahepatic, perihilar, and distal cholangiocarcinoma as well as gallbladder cancer, are rare but aggressive malignancies with few effective standard of care therapies. Methods: We implemented integrative clinical sequencing of advanced BTC tumors from 124 consecutive patients who progressed on standard therapies (N=92 with MI-ONCOSEQ and N=32 with commercial gene panels) enrolled between 2011-2020. Results: Genomic profiling of paired tumor and normal DNA and tumor transcriptome (RNA) sequencing identified actionable somatic and germline genomic alterations in 54 patients (43.5%), and potentially actionable alterations in 79 (63.7%) of the cohort. Of these, patients who received matched targeted therapy (22; 40.7%) had a median overall survival of 28.1 months compared to 13.3 months in those who did not receive matched targeted therapy (32; P < 0.01), or 13.9 months in those without actionable mutations (70; P < 0.01). Additionally, we discovered recurrent activating mutations in FGFR2, and a novel association between KRAS and BRAF mutant tumors with high expression of immune modulatory protein NT5E (CD73) that may represent novel therapeutic avenues. Conclusions: Overall, the identification of actionable/ potentially actionable aberrations in a large proportion of cases, and improvement in survival with precision oncology supports molecular analysis and clinical sequencing for all patients with advanced BTC. Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023. Published by Elsevier Inc.)
Databáze:	MEDLINE
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