Evidence map›Paper›PMID 40742050›Full record

ArticleThe oncologist2025

Investigating incidence of RAS/RAF and PIK3CA alterations in HER2-amplified colorectal cancer: a comprehensive analysis.

Svea Cheng, Cyndi Gonzales Gomez, Morgan Ferrell, Richard Giza, Masood Pasha Syed, Tara Magge, Vikram Gorantla, Ronan W Hsieh, Riyue Bao, Aatur Singhi and 2 more

Abstract read
In one paragraph

Article in The oncologist, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Review
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

12 authors.

Svea ChengUniversity of Pittsburgh School of Medicine, Division of Hematology/Oncology, Pittsburgh, PA 15213, United States.
Cyndi Gonzales GomezDepartment of Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, United States.
Morgan FerrellDepartment of Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, United States.
Richard GizaDepartment of Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, United States.
Masood Pasha SyedDepartment of Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, United States.
Tara MaggeUPMC Hillman Cancer Center, Division of Hematology/Oncology at UPMC Shadyside, Pittsburgh, PA 15232, United States.
Vikram GorantlaUPMC Hillman Cancer Center, Division of Hematology/Oncology at UPMC Shadyside, Pittsburgh, PA 15232, United States.
Ronan W HsiehDivision of Hematology and Oncology, University of Washington School of Medicine, Seattle, WA 98109, United States.
Riyue BaoDepartment of Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, United States.
Aatur SinghiDepartment of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, United States.
Anwaar SaeedDivision of Hematology & Oncology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, United States.
Ibrahim Halil SahinDivision of Hematology & Oncology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, United States.ORCID 0000-0003-2758-3077

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Jessie Nedrow · 1988 to 2026
$158.0M
NCI NIH HHS P30 CA047904NCI NIH HHS P30CA047904University of Pittsburgh S10OD028483
6 · The paper itself

Abstract

backgroundAmplification of human epidermal growth factor receptor-2 (HER2) can be targeted with HER2-directed combination therapies for patients with colorectal cancer (CRC). Evolving data from clinical trials suggest mutations in KRAS and PIK3CA, downstream effectors of HER2, may confer resistance to HER2 blockade. However, the true incidence of these alterations in HER2-amplified CRC is largely unknown. In this large cohort study, we investigated the incidence of RAS/RAF and PIK3CA alterations among patients with HER2-amplified CRC.

methodsTwenty-one studies containing CRC specimens as of April 2023 were sampled using cBioPortal for Cancer Genomics. Clinical, specimen, copy number alteration, and somatic mutation data were aggregated and processed to generate ~30 analysis-ready fields encompassing demographic variables, HER2 amplification, and KRAS/NRAS/PIK3CA/BRAF/MAPK1/MAPK3/HER2 mutations.

resultsAmong 4823 patients with CRC, the incidence of HER2 amplification was 2.6% (87/4823), with a higher incidence in male, Asian, and Black patients. Among patients with HER2-amplified CRC, the incidence of KRAS, NRAS, and PIK3CA mutations was 21.8% (19/87) (27.9% [17/61] in colon cancer, 7.7% [2/26] in rectal cancer), 3.4% (3/87)(3.3% [2/61] in colon cancer, 3.8% [1/26] in rectal cancer), and 11.5% (10/87) (13.1% [8/61] in colon cancer, 7.7% [2/26] in rectal cancer), respectively. No BRAF, MAPK1, or MAPK3 mutations were identified. Notably, concurrent HER2 mutation and amplification occurred at an incidence of 16.1% (14/87) (16.4% [10/61] in colon cancer, 15.4% [4/26] in rectal cancer). Median overall survival for all stage patients was significantly lower in patients with HER2-amplified CRC (37.2 months) than in patients with CRC without HER2 amplification (74.9 months) (P = .038).

conclusionsRAS, PIK3CA, and HER2 mutations can commonly co-occur with HER2 amplification, with higher rates in colon cancer than rectal cancer. These findings underscore biological heterogeneity and the importance of molecular profiling in identifying potential resistance before initiation of HER2-directed therapy.

Indexed as

Class I Phosphatidylinositol 3-KinasesColorectal NeoplasmsErb-b2 Receptor Tyrosine KinasesProto-Oncogene Proteins p21(ras)raf KinasesAdultAgedFemaleGene AmplificationHumansIncidenceMaleMiddle AgedMutationProto-Oncogene Proteins B-rafClass I Phosphatidylinositol 3-KinasesERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesKRAS protein, humanPIK3CA protein, humanProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)raf KinasesBRAFcolorectal cancerHER2 amplificationHER2-directed therapyhuman epidermal growth factor receptor-2KRASPIK3CAresistance mechanisms

Identifiers

PMID40742050
PMCPMC12311930

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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.