Evidence map›Paper›PMID 42360806›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2026

Molecular and Clinical Determinants of Targeted Therapy Treatment in Biliary Tract Cancer.

Darren Cowzer, Henry Walch, Pranita Atri, Farheen Shah, Risha Huq, Rohit Thummalapalli, Fatema Nagib, Anna Varghese, Danny N Khalil, Wungki Park and 17 more

Abstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Cells · 2026
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

27 authors.

Darren CowzerDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0002-0969-3259
Henry WalchKravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0003-1188-350X
Pranita AtriDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0002-0417-0256
Farheen ShahKravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0009-0000-2194-6573
Risha HuqDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0009-0000-0302-7012
Rohit ThummalapalliDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0002-8865-0299
Fatema NagibKravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0009-0002-7202-2519
Anna VargheseDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0001-5426-0885
Danny N KhalilDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0003-4688-0958
Wungki ParkDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0002-8006-3102
Benoit RousseauDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0002-1594-4827
Andrea CercekDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0002-5054-8192
Joseph ErinjeriWeill Medical College of Cornell University, New York, New York.ORCID 0000-0003-1876-727X
Randy YehDepartment of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0003-2945-5546
Richard K DoDepartment of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0002-6554-0310
Olca BasturkWeill Medical College of Cornell University, New York, New York.ORCID 0000-0003-2747-1366
Jinru ShiaWeill Medical College of Cornell University, New York, New York.ORCID 0000-0002-4351-2511
Debyani ChakravartyKravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0001-8629-5732
Michael F BergerKravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0003-3882-5000
Nikolaus SchultzKravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0002-0131-4904
Mithat GonenDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0001-8683-8477
Eileen M O'ReillyDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0002-8076-9199
William JarnaginWeill Medical College of Cornell University, New York, New York.ORCID 0000-0002-1635-5768
Ghassan K Abou-AlfaDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0002-1522-8054
David B SolitDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0002-6614-802X
Walid K Chatila *Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0001-5474-218X
James J Harding *Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0002-7029-4310

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
HER2 PET imaging to assess HER2 heterogeneity and predict response to HER2-targeted therapy in biliary tract cancerR01CA309345 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Mark P. Dunphy, James J Harding · 2026 to 2026
$715k
Cycle for SurvivalMemorial Sloan Kettering Cancer Center Experimental Therapeutics CenterNational Cancer Institute (NCI) P30 CA008748National Cancer Institute (NCI) R01CA309345NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA309345Society of Memorial Sloan Kettering (Society of MSK)
6 · The paper itself

Abstract

purposeActionable genomic alterations occur in all anatomic subsets of biliary tract cancer; however, targeted therapies have not shown a survival advantage over cytotoxics, and resistance mechanisms require further characterization. EXPERIMENTAL

designWe analyzed a prospectively maintained cohort of 1,254 patients with histologically confirmed biliary tract cancer who underwent molecular profiling using an FDA-authorized targeted next-generation sequencing (NGS) assay. We defined actionable alterations across anatomic subsets, compared outcomes with targeted therapy versus cytotoxics, and evaluated genomic correlates of resistance using longitudinal samples.

resultsOverall, 59% of patients harbored at least one OncoKB alteration, and 32.2% (intrahepatic 40%, extrahepatic 15%, and gallbladder 22%) had a level 1/2 alteration. Emerging targets included KRAS alterations (17%), MTAP deletions (12.8%), MDM2 amplification (6.5%), and MET amplification (1.5%). Targeted therapy was associated with improved progression-free survival but not overall survival. Co-occurring TP53/RAS pathway and SMAD4 alterations were associated with inferior outcomes in IDH1/FGFR2-and ERBB2-driven tumors, respectively. Longitudinal profiling demonstrated ERBB2 loss in ERBB2-driven tumors, whereas IDH-, FGFR-, BRAF-, and NTRK-driven tumors retained the primary oncogenic driver. Acquired resistance was associated with alterations in RAS, MEK, MET, MYC, and CDKN2A.

conclusionsThis comprehensive molecular profiling study illustrates the real-world utility and limitations of targeted NGS of biliary tract cancer and affirms the use of precision medicine in patients with these diseases. Genomic heterogeneity and therapeutic resistance observed in this study has the potential to inform ongoing drug development efforts for biliary tract cancer.

Indexed as

Biliary Tract NeoplasmsBiomarkers, TumorMolecular Targeted TherapyAdultAgedAged, 80 and overDrug Resistance, NeoplasmFemaleHigh-Throughput Nucleotide SequencingHumansMaleMiddle AgedMutationPrognosisBiomarkers, Tumor

Identifiers

PMID42360806
PMCPMC13420548

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.