Evidence map›Paper›PMID 39317818›Full record

ReviewNature reviews. Clinical oncology2024

Neoadjuvant immunotherapy for dMMR and pMMR colorectal cancers: therapeutic strategies and putative biomarkers of response.

Christopher J M Williams, Allyson M Peddle, Pashtoon M Kasi, Jenny F Seligmann, Campbell S Roxburgh, Gary W Middleton, Sabine Tejpar

Erratum issuedAbstract readReview
PubMed Publisher
In one paragraph

Review in Nature reviews. Clinical oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 64 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed, 3 pooled it
–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

64 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
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  12. Universal off-the-shelf TGF-Acta pharmaceutica Sinica. B · 2026
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4 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Christopher J M Williams *Division of Oncology, Leeds Institute of Medical Research, University of Leeds, Leeds, UK. c.williams1@leeds.ac.uk.ORCID http://orcid.org/0000-0002-1574-653X
Allyson M Peddle *Department of Oncology, KU Leuven, Leuven, Belgium. ally.peddle@kuleuven.be.
Pashtoon M KasiDepartment of Gastrointestinal Oncology, City of Hope Orange County Lennar Foundation Cancer Center, Irvine, CA, USA.
Jenny F SeligmannDivision of Oncology, Leeds Institute of Medical Research, University of Leeds, Leeds, UK.
Campbell S RoxburghSchool of Cancer Sciences, University of Glasgow, Glasgow, UK.
Gary W MiddletonInstitute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
Sabine TejparDepartment of Oncology, KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0003-3281-8643

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Approximately 15% of locally advanced colorectal cancers (CRC) have DNA mismatch repair deficiency (dMMR), resulting in high microsatellite instability and a high tumour mutational burden. These cancers are frequently sensitive to therapy with immune-checkpoint inhibitors (ICIs) in the metastatic setting. This sensitivity seems to be even more pronounced in locally advanced disease, and organ preservation has become a realistic aim in ongoing clinical trials involving patients with dMMR rectal cancer. By contrast, metastatic CRCs with proficient DNA mismatch repair (pMMR) are generally resistant to ICIs, although a proportion of locally advanced pMMR tumours seem to have a high degree of sensitivity to ICIs. In this Review, we describe the current and emerging clinical evidence supporting the use of neoadjuvant ICIs in patients with dMMR and pMMR CRC, and the potential advantages (based on a biological rationale) of such an approach. We discuss how neoadjuvant 'window-of-opportunity' trials are being leveraged to progress biomarker discovery and we provide an overview of potential predictive biomarkers of response to ICIs, exploring the challenges faced when evaluating such biomarkers in biopsy-derived samples. Lastly, we describe how these discoveries might be used to drive a rational approach to trialling novel immunotherapeutic strategies in patients with pMMR CRC, with the ultimate aim of disease eradication and the generation of long-term immunosurveillance.

Indexed as

Biomarkers, TumorColorectal NeoplasmsDNA Mismatch RepairImmune Checkpoint InhibitorsImmunotherapyNeoadjuvant TherapyHumansMicrosatellite InstabilityBiomarkers, TumorImmune Checkpoint Inhibitors

Identifiers

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.