Rectal Adenocarcinoma (READ)

Overview

Rectal adenocarcinoma (READ) is a malignant epithelial tumor arising in the rectum. On OncoTree it sits under the COADREAD (colorectal) lineage. Neoadjuvant short-course radiotherapy (SCRT; 25 Gy/5 fractions) is an established standard-of-care approach and serves as an active model for studying RT-immune system interactions. Key research questions include the extent to which radiation reshapes the tumor immune microenvironment, the microbiome, and systemic immunity.

Cohorts in the corpus

  • ROBIN ImmunoRad MCT1 (NCT05943210) — 39/50 enrolled (10 academic centers in U.S. and Europe, including Weill Cornell Medicine, MSKCC, University of Chicago, Rutgers, Cedars-Sinai, ICR/Royal Marsden, Glasgow, Manchester, Leeds, Gustave Roussy); preoperative SCRT with longitudinal biospecimen collection (tissue biopsies, blood, stool); 140+ tissue samples banked and processed for 10x Genomics Visium HD spatial transcriptomics. PMID:41941260
  • ROBIN ImmunoRad MCT2 (NCT05024097) — Phase I/II SCRT (25 Gy/5 fractions) + etrumadenant (dual A2AR/A2BR adenosine antagonist) + zimberelimab (anti-PD-1) + FOLFOX in rectal cancer; 21 enrolled; Simon’s 2-stage design (27 evaluable patients) powered to detect CR rate ≥45% vs. null ≤25%. PMID:41941260

Recurrent alterations

No gene-level variant claims are made in the corpus for READ specifically; studies are at the translational/MCT-design stage. - In 69 matched MSS colorectal cancer trios (16% rectal primary), rectal tumors showed the same high primary-metastasis concordance for driver mutations (KRAS, NRAS, BRAF) as colon tumors; metastasis-private RTK-RAS events (MAP2K1 Q56P, EGFR amplification) were identified in RAS/RAF wild-type cases. PMID:25164765 - READ was included in the MSK-IMPACT pan-cancer cohort (msk_impact_2017) spanning 62 principal tumor types; POLE and MMR mutation signatures were enriched in colorectal lineages including READ, with MSI tumors showing responses to immune checkpoint blockade. PMID:28481359 - Rectal adenocarcinoma was part of the 1,134-sample colorectal MSK-IMPACT cohort; TP53 was the only gene enriched in metastatic vs early-stage CRC; WNT pathway alteration rose to 96% of all CRCs with extended calling PMID:29316426 - MC3 pan-cancer mutation-calling project (10,510 TCGA pairs) included READ; concordance with PanCan12 MAF exceeded 90% PMID:29596782 - Pan-cancer fusion study (9,624 TCGA samples) included READ as part of the COADREAD gastrointestinal cluster PMID:29617662 - Pan-cancer aneuploidy study placed READ in the gastrointestinal arm-level cluster alongside COAD, STAD, and PAAD; READ and COAD are exceptions to the positive aneuploidy–mutation-rate correlation due to MSI-high and POLE-mutant cases PMID:29622463

Subtypes

No molecular subtyping data from the corpus specific to READ yet.

Therapeutic landscape

  • ROBIN ImmunoRad center (U54 CA274291; Weill Cornell Medicine + 9 collaborating centers) investigates RT-immune system interactions in rectal cancer as a model tumor. SCRT was chosen as an optimal model because it provides a standalone RT intervention for mechanistic study. PMID:41941260
  • RT + etrumadenant + zimberelimab + FOLFOX (MCT2, NCT05024097): preliminary CR rate was 1/5 (20%) in Part I (safety run-in); in Part II, 11/15 stage-1 patients (82%) completed treatment and achieved CR — the trial is anticipated to proceed to stage 2 to accrue 12 additional patients. PMID:41941260
  • Spatial transcriptomics (Visium HD) on 140+ MCT1 biopsies identified RT-associated spatial reorganization of lymphocytes and altered macrophage wound-healing signals. scRNA-seq of pre/post-RT PBMCs showed MYC-driven activation in CD8+ T cells, ECM-remodeling in monocytes, and stress responses in B cells — interpreted as RT-induced systemic trained immunity. 16S/ITS microbiome sequencing revealed post-RT increases in Clostridiales and Trichocomaceae. PMID:41941260

Sources

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This page was processed by crosslinker on 2026-05-04. - PMID:25164765

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This page was processed by entity-page-writer on 2026-05-15. - PMID:29596782

This page was processed by wiki-cli on 2026-05-15. - PMID:29617662

This page was processed by wiki-cli on 2026-05-15. - PMID:29622463

This page was processed by wiki-cli on 2026-05-15.