Evidence mapPaperPMID 42481817Full record

ReviewCancer metastasis reviews2026

From bench to bedside: advancing our understanding of radioresistance in rectal cancer.

Diogo Estêvão, Miguel da Cruz-Ribeiro, Diogo Coelho, Joana Lencart, Olga Sousa, Bruno Sarmento, Olivier de Wever, Maria J Oliveira, Tânia Cruz

Abstract readReview
In one paragraph

Review in Cancer metastasis reviews, 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

9 authors.

Diogo Estêvãoi3S - Institute for Research and Innovation in Health, University of Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal.ORCID http://orcid.org/0000-0001-6457-2356
Miguel da Cruz-Ribeiroi3S - Institute for Research and Innovation in Health, University of Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal.ORCID http://orcid.org/0000-0001-5630-8635
Diogo Coelhoi3S - Institute for Research and Innovation in Health, University of Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal.ORCID http://orcid.org/0000-0002-7424-1830
Joana LencartMedical Physics, Radiobiology and Radiation Protection Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal.ORCID http://orcid.org/0000-0001-7078-7257
Olga SousaDepartment of Radiotherapy, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal.
Bruno Sarmentoi3S - Institute for Research and Innovation in Health, University of Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal.ORCID http://orcid.org/0000-0001-5763-7553
Olivier de WeverLaboratory of Experimental Cancer Research, Department of Human Structure and Repair, Ghent University, Ghent, Belgium.ORCID http://orcid.org/0000-0002-5453-760X
Maria J Oliveirai3S - Institute for Research and Innovation in Health, University of Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal. mariajo@ineb.up.pt.ORCID http://orcid.org/0000-0002-0724-0272
Tânia Cruzi3S - Institute for Research and Innovation in Health, University of Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal.ORCID http://orcid.org/0000-0001-7051-040X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The global incidence of rectal cancer (RC) is increasing at an alarming rate, with over 50% of cases still diagnosed at advanced stages, despite improvements in early detection. While neoadjuvant (chemo)radiotherapy regimens remain a cornerstone of treatment, up to 20-40% of tumours exhibit or develop resistance to ionising radiation, limiting therapeutic options and leading to disease evolution. This review offers a comprehensive insight into the complex biological and molecular mechanisms underlying RC radioresistance within the fundamental 6Rs of radiobiology: Repair, Reoxygenation, Redistribution, Radiosensitivity, Repopulation, and Reactivation. More specifically, DNA damage repair pathways, cell cycle regulation, hypoxia, transcriptional plasticity regulators such as cancer stem cells, and non-coding RNAs are comprehensively reviewed. Additionally, the critical roles of tumour-infiltrating lymphocytes, cancer-associated macrophages, and inflammatory cancer-associated fibroblasts in radioresistance are also dissected, which collectively shape an immunosuppressive and pro-metastatic niche following radiotherapy. Furthermore, a less explored mechanism, namely the metabolic rewiring of cancer cells after radiotherapy, is proposed as a new 7th R of Radiobiology, namely "Reprogramming", that enables tumour survival and promotes aggressive phenotypes. This new perspective adds a new layer of complexity to the molecular understanding of RC resistance and provides a mechanistic insight currently missing in radiobiology research. Additionally, advanced experimental models, such as spheroids, patient-derived organoids, and animal models, are discussed as valuable platforms for pre-clinical research and therapeutic testing. This review also integrates mechanistic insights with biomarker-guided clinical decision-making to support RC management. By unravelling these multifactorial mechanisms, we highlight opportunities to develop predictive biomarkers and tailored therapeutic strategies to overcome resistance and improve patient outcomes.

Indexed as

Radiation ToleranceRectal NeoplasmsAnimalsHumansNeoplastic Stem CellsTranslational Research, BiomedicalMetabolic rewiringRadiobiology RsRadioresistanceRectal cancer

Identifiers

PMID42481817
PMCPMC13388369

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.