Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.0field-weighted citation impact, top 12% of its field
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
8 citing papers in PubMed, 7 citations in OpenAlex.
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
42 authors at 8 institutions in 2 countries.
Harshabad SinghDana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0001-6295-2013
Pranshu SahgalDana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-9857-3987
Kevin KapnerDana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-2306-2373
Steven M CorselloDepartment of Medicine, Stanford University, Palo Alto, California.ORCID 0000-0002-9929-3709
Hersh GuptaDana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-5136-6403
Rahul GujrathiDepartment of Radiology, Boston Medical Center and Boston University, Boston, Massachusetts.ORCID 0000-0003-2581-2315
Yvonne Y LiDana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-1741-1995
Andrew D CherniackDana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0003-0470-0111
Raquelle El AlamDepartment of Radiology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-4296-6095
Joseph KerfootDepartment of Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0009-0001-3517-3951
Elizabeth AndrewsDana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0009-0008-9117-6736
Annette LeeDana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0009-0001-1039-706X
Chetan NambiarDana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0009-0003-1817-2628
Alison M HanniganDana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0009-0004-3232-0460
Joshua RemlandDana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0009-0004-5655-0762
Lauren BraisDana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0003-1069-0407
Meghan E LeahyDana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0009-0001-8453-7416
Douglas A RubinsonDana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-5337-5231
Benjamin L SchlechterDana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-1529-3278
Matthew MeyersonDana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-9133-8108
Yanan KuangBelfer Center for Applied Cancer Science, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-5416-5543
Cloud P PaweletzBelfer Center for Applied Cancer Science, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-2287-5663
Andrew J AguirreDana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-0701-6203
Kimberly J PerezDana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-5745-2994
Brandon M HuffmanDana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-0768-3145
Humberto RossiDana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0009-0006-5141-0132
Thomas A AbramsDana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0003-3101-1573
Sheheryar KabrajiDana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-5315-7103
Livio TrusolinoCandiolo Cancer Institute FPO IRCCS, Candiolo, Torino, Italy.ORCID 0000-0002-6379-3365
Andrea BertottiCandiolo Cancer Institute FPO IRCCS, Candiolo, Torino, Italy.ORCID 0000-0001-8196-7608
Ewa T SicinskaDepartment of Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0003-2564-3478
Aparna R ParikhMassachusetts General Hospital Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-5245-7841
Brian M WolpinDana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-0455-1032
Marios GiannakisDana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0001-9012-6982
Kimmie NgDana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0003-0631-1494
Jeffrey A MeyerhardtDana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-1120-0898
Jason L HornickDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.ORCID 0000-0001-6475-8345
Nilay S SethiDana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-3748-7559
James M ClearyDana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0001-7213-3951
Dana-Farber Cancer Institute · USBroad Institute · USGlobalFoundries (United States) · USTorino e-district · ITBoston Medical Center · USBrigham and Women's Hospital · USMassachusetts General Hospital · USPalo Alto University · US
Funding
Tissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI SHIVDASANI, RAMESH A · 2007 to 2023
$33.2M
Novel randomized controlled trials of vitamin D supplementation in patients with colorectal cancer: Impact on survival and biologyR01CA205406 · NCI · DANA-FARBER CANCER INST · PI Kimmie Ng · 2017 to 2026
$4.9M
Mechanisms of response and resistance to KRAS inhibition in pancreatic cancerR01CA276268 · NCI · DANA-FARBER CANCER INST · PI Andrew James Aguirre · 2023 to 2026
$2.2M
Improving response prediction to neoadjuvant therapy in pancreatic cancerK08CA286749 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Harshabad Singh · 2023 to 2026
$1.2M
Targeting casein kinase 1-alpha for cancer therapyK08CA230220 · NCI · STANFORD UNIVERSITY · PI CORSELLO, STEVEN MUNTEAN · 2018 to 2022
$1.0M
Integration of early genetic alterations and inflammation in gastroesophageal premalignancyK08DK120930 · NIDDK · DANA-FARBER CANCER INST · PI SETHI, NILAY · 2019 to 2023
purposeERBB2-amplified colorectal cancer is a distinct molecular subtype with expanding treatments. Implications of concurrent oncogenic RAS/RAF alterations are not known. EXPERIMENTAL
designDana-Farber and Foundation Medicine Inc. Colorectal cancer cohorts with genomic profiling were used to identify ERBB2-amplified cases [Dana-Farber, n = 47/2,729 (1.7%); FMI, n = 1857/49,839 (3.7%)]. Outcomes of patients receiving HER2-directed therapies are reported (Dana-Farber, n = 9; Flatiron Health-Foundation Medicine clinicogenomic database, FH-FMI CGDB, n = 38). Multisite HER2 IHC and genomic profiling were performed to understand HER2 intratumoral and interlesional heterogeneity. The impact of concurrent RAS comutations on the effectiveness of HER2-directed therapies were studied in isogenic colorectal cancer cell lines and xenografts.
resultsERBB2 amplifications are enriched in left-sided colorectal cancer. Twenty percent of ERBB2-amplified colorectal cancers have co-occurring oncogenic RAS/RAF alterations. While RAS/RAF WT colorectal cancers typically have clonal ERBB2 amplification, colorectal cancers with co-occurring RAS/RAF alterations have lower level ERRB2 amplification, higher intratumoral heterogeneity, and interlesional ERBB2 discordance. These distinct genomic patterns lead to differential responsiveness and patterns of resistance to HER2-directed therapy. ERBB2-amplified colorectal cancer with RAS/RAF alterations are resistant to trastuzumab-based combinations, such as trastuzumab/tucatinib, but retain sensitivity to trastuzumab deruxtecan in in vitro and murine models. Trastuzumab deruxtecan shows clinical efficacy in cases with high-level ERBB2-amplified RAS/RAF coaltered colorectal cancer.
conclusionsCo-occurring RAS/RAF alterations define a unique subtype of ERBB2-amplified colorectal cancer that has increased intratumoral heterogeneity, interlesional discordance, and resistance to trastuzumab-based combinations. Further examination of trastuzumab deruxtecan in this previously understudied cohort of ERBB2-amplified colorectal cancer is warranted.
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.
RAS/RAF Comutation and ERBB2 Copy Number Modulates HER2 Heterogeneity and Responsiveness to HER2-directed Therapy in Colorectal Cancer. · full record | OpenQuestion