Evidence map›Paper›PMID 42897222›Full record

ArticleOncogene2026

Activation of the endocytosis pathway stratifies subtypes and therapeutic sensitivity in colorectal cancer.

Hiroyuki Arai, Andrew Elliott, Yan Yang, Alex Farrell, Joshua Millstein, Fang-Shu Ou, Federico Innocenti, Jingyuan Wang, Francesca Battaglin, Priya Jayachandran and 15 more

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

25 authors.

Hiroyuki AraiDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-1886-7070
Andrew ElliottClinical & Translational Research, Medical Affairs, Caris Life Sciences, Phoenix, AZ, USA.ORCID http://orcid.org/0000-0001-8494-8031
Yan YangDepartment of Population and Public Health Sciences, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-7883-0798
Alex FarrellClinical & Translational Research, Medical Affairs, Caris Life Sciences, Phoenix, AZ, USA.
Joshua MillsteinDepartment of Population and Public Health Sciences, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0001-7961-8943
Fang-Shu OuAlliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0003-1267-8735
Federico InnocentiUNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Jingyuan WangDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.ORCID http://orcid.org/0009-0006-6931-0359
Francesca BattaglinDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Priya JayachandranDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.ORCID http://orcid.org/0009-0002-2480-4057
Sandra AlgazeDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Shivani SoniDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Wu ZhangDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Richard M GoldbergWest Virginia University Cancer Institute, Morgantown, WV, USA.ORCID http://orcid.org/0000-0003-0308-8223
Michael J HallDepartment of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA.
Aaron James ScottDivision of hematology/oncology, University of Arizona Cancer Center, Tucson, AZ, USA.
Jimmy J HwangDepartment of Solid Tumor Oncology, GI Medical Oncology, Levine Cancer Institute, Charlotte, NC, USA.
Emil LouDivision of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA.ORCID http://orcid.org/0000-0002-1607-1386
Benjamin A WeinbergRuesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
John MarshallRuesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
Sanjay GoelDepartment of Medical Oncology, Rutgers Cancer Institute, New Brunswick, NJ, USA.ORCID http://orcid.org/0000-0002-2798-7568
Joanne XiuClinical & Translational Research, Medical Affairs, Caris Life Sciences, Phoenix, AZ, USA.
W Michael KornClinical & Translational Research, Medical Affairs, Caris Life Sciences, Phoenix, AZ, USA.
Alan P VenookUniversity of California, San Francisco, San Francisco, CA, USA.
Heinz-Josef LenzDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. lenz@usc.edu.ORCID http://orcid.org/0000-0003-2178-9568

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026
$181.4M
U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) P30CA014089
6 · The paper itself

Abstract

Endocytosis regulates receptor trafficking and signaling, yet its role in colorectal cancer (CRC) remains unclear. We analyzed transcriptomic data from 15,025 CRC tumors to evaluate gene expression in clathrin-mediated endocytosis (CME) and the endosomal sorting complexes required for transport (ESCRT) pathway. Pathway-level signatures were compared across consensus molecular subtypes (CMS) and examined in relation to oncogenic signaling programs, while individual endocytosis-related genes were evaluated for associations with clinical outcomes in an independent randomized trial cohort. Expression of CME and ESCRT pathways varied by CMS, with the highest expression in CMS4 and the lowest in CMS3. Endocytosis signatures correlated with multiple oncogenic signaling pathways, including MAPK, TGF-β, WNT, PI3K, NOTCH, and angiogenesis, suggesting broad links between endocytic activity and tumor biology. In the randomized phase III CALGB/SWOG 80405 trial, low expression of AP2M1-a core adaptor in the CME complex-was significantly associated with longer overall survival and progression-free survival in patients treated with anti-EGFR agents, but not in those receiving anti-VEGF agents. These findings suggest that endocytic trafficking may be associated with oncogenic signaling and differential therapeutic benefit in patients with metastatic CRC. The endocytosis pathway reflects biologically relevant heterogeneity in CRC and may help guide therapeutic stratification.

Identifiers

PMID42897222

What OpenQuestion holds

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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.