Rectum adenocarcinoma

Summary

Rectum adenocarcinoma (MONDO:0002169) is a disease with 1 cohort gene and 157 clinical trials. Top therapeutic interventions include fluorouracil, tipiracil, and leucovorin.

At a glance

• Cohort genes: 1
• ClinVar variants: 4
• Clinical trials: 157

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	rectum adenocarcinoma
Mondo ID	MONDO:0002169
EFO	EFO:0005631
DOID	DOID:1996
ICD-11	1316028436
NCIT	C9383
SNOMED CT	254582000
UMLS	C0149978
MedGen	56214
Anatomy (UBERON)	UBERON:0001052
Is cancer (heuristic)	no

Also known as: adenocarcinoma - rectum · adenocarcinoma of rectum · adenocarcinoma of the rectum · read · rectal adenocarcinoma · rectum adenocarcinoma

Data availability: 4 ClinVar variants · 83 cell lines · 15 intOGen driver records.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › carcinoma › adenocarcinoma › colorectal adenocarcinoma › rectum adenocarcinoma

Related subtypes (4): colon adenocarcinoma, colorectal serrated adenocarcinoma, colorectal medullary carcinoma, colorectal signet ring cell carcinoma

Subtypes (4): anus adenocarcinoma, rectum mucinous adenocarcinoma, rectal signet ring cell adenocarcinoma, rectal medullary carcinoma

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

4 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
232098	NM_000038.6(APC):c.1984C>A (p.Leu662Ile)	APC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
141061	NM_000038.6(APC):c.811A>G (p.Met271Val)	APC	Uncertain significance	criteria provided, multiple submitters, no conflicts
559958	NM_000038.6(APC):c.6152A>G (p.Lys2051Arg)	APC	Uncertain significance	criteria provided, single submitter
559960	NM_000038.6(APC):c.3160C>T (p.His1054Tyr)	APC	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
APC	Orphanet:220460	Attenuated familial adenomatous polyposis
APC	Orphanet:261584	5q22 microdeletion syndrome
APC	Orphanet:314022	Gastric adenocarcinoma and proximal polyposis of the stomach
APC	Orphanet:3258	Cenani-Lenz syndrome
APC	Orphanet:873	Desmoid tumor

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
APC	HGNC:583	ENSG00000134982	P25054	Adenomatous polyposis coli protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
APC	Adenomatous polyposis coli protein	Tumor suppressor.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
APC	Other/Unknown	no		Armadillo, APC_rpt, SAMP

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
medial globus pallidus	1
substantia nigra pars compacta	1
substantia nigra pars reticulata	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
APC	297	ubiquitous	marker	substantia nigra pars compacta, substantia nigra pars reticulata, medial globus pallidus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
APC	2,903

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
APC	P25054	31

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 31. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
APC truncation mutants are not K63 polyubiquitinated	1	11420.0×	0.003	APC
Signaling by AXIN mutants	1	1038.2×	0.003	APC
Signaling by CTNNB1 phospho-site mutants	1	1038.2×	0.003	APC
Signaling by APC mutants	1	1038.2×	0.003	APC
Signaling by AMER1 mutants	1	1038.2×	0.003	APC
APC truncation mutants have impaired AXIN binding	1	815.7×	0.003	APC
AXIN missense mutants destabilize the destruction complex	1	815.7×	0.003	APC
Truncations of AMER1 destabilize the destruction complex	1	815.7×	0.003	APC
Signaling by GSK3beta mutants	1	761.3×	0.003	APC
CTNNB1 S33 mutants aren’t phosphorylated	1	761.3×	0.003	APC
CTNNB1 S37 mutants aren’t phosphorylated	1	761.3×	0.003	APC
CTNNB1 S45 mutants aren’t phosphorylated	1	761.3×	0.003	APC
CTNNB1 T41 mutants aren’t phosphorylated	1	761.3×	0.003	APC
Beta-catenin phosphorylation cascade	1	671.8×	0.003	APC
Signaling by WNT in cancer	1	601.0×	0.003	APC
Apoptotic cleavage of cellular proteins	1	475.8×	0.004	APC
Apoptotic execution phase	1	475.8×	0.004	APC
Disassembly of the destruction complex and recruitment of AXIN to the membrane	1	356.9×	0.005	APC
Ovarian tumor domain proteases	1	278.5×	0.006	APC
Deactivation of the beta-catenin transactivating complex	1	233.1×	0.007	APC
Degradation of beta-catenin by the destruction complex	1	173.0×	0.008	APC
Apoptosis	1	167.9×	0.008	APC
Programmed Cell Death	1	146.4×	0.009	APC
Deubiquitination	1	124.1×	0.010	APC
TCF dependent signaling in response to WNT	1	117.7×	0.011	APC
Signaling by WNT	1	112.0×	0.011	APC
Diseases of signal transduction by growth factor receptors and second messengers	1	56.8×	0.020	APC
Post-translational protein modification	1	19.2×	0.058	APC
Disease	1	13.1×	0.082	APC
Metabolism of proteins	1	12.4×	0.084	APC

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of microtubule-based movement	1	2808.7×	0.003	APC
negative regulation of cell cycle G1/S phase transition	1	2407.4×	0.003	APC
positive regulation of protein localization to centrosome	1	2407.4×	0.003	APC
negative regulation of cyclin-dependent protein serine/threonine kinase activity	1	2106.5×	0.003	APC
regulation of microtubule-based process	1	1872.4×	0.003	APC
regulation of attachment of spindle microtubules to kinetochore	1	1685.2×	0.003	APC
heart valve development	1	1532.0×	0.003	APC
positive regulation of pseudopodium assembly	1	1296.3×	0.003	APC
endocardial cushion morphogenesis	1	842.6×	0.004	APC
mitotic spindle assembly checkpoint signaling	1	561.7×	0.005	APC
cell fate specification	1	526.6×	0.005	APC
negative regulation of microtubule depolymerization	1	495.6×	0.005	APC
pattern specification process	1	468.1×	0.005	APC
negative regulation of G1/S transition of mitotic cell cycle	1	358.6×	0.006	APC
bicellular tight junction assembly	1	330.4×	0.006	APC
mitotic cytokinesis	1	259.3×	0.007	APC
insulin receptor signaling pathway	1	221.7×	0.008	APC
positive regulation of protein catabolic process	1	203.0×	0.008	APC
positive regulation of cold-induced thermogenesis	1	163.6×	0.010	APC
negative regulation of canonical Wnt signaling pathway	1	117.8×	0.013	APC
protein-containing complex assembly	1	113.9×	0.013	APC
Wnt signaling pathway	1	99.7×	0.014	APC
positive regulation of cell migration	1	61.7×	0.020	APC
cell migration	1	61.5×	0.020	APC
positive regulation of apoptotic process	1	56.7×	0.021	APC
DNA damage response	1	53.5×	0.021	APC
proteasome-mediated ubiquitin-dependent protein catabolic process	1	52.2×	0.021	APC
nervous system development	1	45.9×	0.023	APC
negative regulation of cell population proliferation	1	42.1×	0.025	APC
cell adhesion	1	37.5×	0.027	APC

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
APC	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
APC	24	Binding:24

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	APC

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
APC	24	—

Clinical trials & evidence

Clinical trials

Clinical trials: 157.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	58
Not specified	48
PHASE1	24
PHASE1/PHASE2	12
PHASE3	10
PHASE2/PHASE3	2
EARLY_PHASE1	2
PHASE4	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04281667	PHASE4	ACTIVE_NOT_RECRUITING	Mechanical Bowel Preparation and Oral Antibiotics Versus Mechanical Bowel Preparation Only Prior Rectal Surgery
NCT02945566	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Can We Save the Rectum by Watchful Waiting or TransAnal Surgery Following (chemo)Radiotherapy Versus Total Mesorectal Excision for Early REctal Cancer?
NCT05482516	PHASE3	RECRUITING	Evaluating Novel Therapies in ctDNA Positive GI Cancers
NCT06997497	PHASE3	RECRUITING	A Clinical Study of Calderasib (MK-1084) With Targeted Therapy and Chemotherapy in People With Colorectal Cancer (MK-1084-012/KANDLELIT-012)
NCT07118800	PHASE3	NOT_YET_RECRUITING	Study Evaluating Two Treatment Strategies for Rectal Cancer in Patients ≥75 Years Old
NCT07549399	PHASE3	NOT_YET_RECRUITING	SCRT + Chemo Targeted Immuno-neoadjuvant Therapy for High-risk pMMR/MSS RC
NCT07596290	PHASE2/PHASE3	NOT_YET_RECRUITING	Yang et al. Anti-PD-1/CTLA-4 Dual Immunotherapy for LARC
NCT00003873	PHASE3	COMPLETED	Fluorouracil With or Without Eniluracil in Treating Patients With Advanced Colorectal Cancer
NCT00025337	PHASE3	COMPLETED	Combination Chemotherapy With or Without Bevacizumab Compared With Bevacizumab Alone in Treating Patients With Advanced or Metastatic Colorectal Cancer That Has Been Previously Treated
NCT00070122	PHASE3	TERMINATED	Combination Chemotherapy and Bevacizumab in Treating Patients With Locally Advanced, Metastatic, or Recurrent Colorectal Cancer
NCT00145769	PHASE3	COMPLETED	A Randomised Trial of Preoperative Radiotherapy for Stage T3 Adenocarcinoma of Rectum
NCT00303628	PHASE3	TERMINATED	Postoperative Chemotherapy With or Without Bevacizumab for Patients With Stage II or III Rectal Cancer
NCT02314182	PHASE3	COMPLETED	GRECCAR 8: Primary Tumor Resection in Rectal Cancer With Unresectable Metastasis
NCT02688712	PHASE2	ACTIVE_NOT_RECRUITING	ExIST Study of LY2157299 (Galunisertib) in Rectal Cancer
NCT04017650	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Encorafenib, Cetuximab, and Nivolumab in Treating Patients With Microsatellite Stable, BRAFV600E Mutated Unresectable or Metastatic Colorectal Cancer
NCT04165772	PHASE2	RECRUITING	Study of Induction PD-1 Blockade in Subjects With Locally Advanced Mismatch Repair Deficient Solid Tumors
NCT04599140	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	SX-682 and Nivolumab for the Treatment of RAS-Mutated, MSS Unresectable or Metastatic Colorectal Cancer, the STOPTRAFFIC-1 Trial
NCT04616183	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	LY3214996 and Cetuximab Alone or in Combination With Abemaciclib for the Treatment of Unresectable or Metastatic Colorectal Cancer
NCT04751370	PHASE2	ACTIVE_NOT_RECRUITING	Testing Nivolumab and Ipilimumab With Short-Course Radiation in Locally Advanced Rectal Cancer
NCT04963283	PHASE2	ACTIVE_NOT_RECRUITING	Study of Cabozantinib and Nivolumab in Refractory Metastatic Microsatellite Stable (MSS) Colorectal Cancer
NCT05308446	PHASE2	ACTIVE_NOT_RECRUITING	Testing the Addition of Nivolumab to Standard Treatment for Patients With Metastatic or Unresectable Colorectal Cancer That Have a BRAF Mutation
NCT05627635	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	FOLFOX and Bevacizumab in Combination With Botensilimab and Balstilimab (3B-FOLFOX) for the Treatment of Microsatellite Stable (MSS) Metastatic Colorectal Cancer
NCT05672524	PHASE2	RECRUITING	A Study of Tucatinib and Trastuzumab in People With Rectal Cancer
NCT06266832	PHASE2	RECRUITING	The Efficacy and Safety of Short-course Radiation Combined With Adebrelimab and CAPEOX Neo-adjuvant Therapy for Organ-retention in Patients With MSS/pMMR Ultra Low Rectal Adenocarcinoma
NCT06569368	PHASE2	RECRUITING	Trial Utilizing Metronidazole to Optimize the Microbiome of Rectal Adenocarcinoma Undergoing Neoadjuvant Therapy
NCT06780787	PHASE2	RECRUITING	FOLFOX, Botensilimab, and Balstilimab for the Treatment of Localized Rectal Cancer Before Surgery
NCT06783153	PHASE1/PHASE2	NOT_YET_RECRUITING	Efficacy and Safety of Adjunctive Use of Rifaximin In Preventing Radiotherapy-induced Diarrhea in Cancer Patients
NCT06843434	PHASE2	RECRUITING	A Study of Botensilimab and Balstilimab for Rectal Adenocarcinoma
NCT06872606	PHASE2	NOT_YET_RECRUITING	Short-Course Radiotherapy Combined with Intracavitary Brachytherapy Followed by Pucotenlimab, Bevacizumab, Oxaliplatin, and Trifluridine/Tipiracil (TAS-102) for Total Neoadjuvant Therapy of Microsatellite Stable (MSS) Locally Advanced Low Rectal Cancer
NCT06908031	PHASE2	RECRUITING	SCRT + mFOLFOX6 + PD-1 Antibody + Targeted Therapy for HIgh-Risk pMMR/MSS Rectal Cancer
NCT06919510	PHASE2	NOT_YET_RECRUITING	A Phase ll Study of Neoadjuvant Short-course Radiotherapy Followed by Ivonescimab and Chemotherapy in pMMR/MSS Locally Advanced Rectal Cancer
NCT07161115	PHASE2	NOT_YET_RECRUITING	Involve-site Radiotherapy Combined With Chemotherapy and Immunotherapy as Neoadjuvant Treatment for Locally Advanced Rectal Cancer
NCT07198165	PHASE2	RECRUITING	SCRT Followed by CAPOX + Bev ± PD-1 Inhibitor for TNT in LARC
NCT07200141	PHASE2	NOT_YET_RECRUITING	Simultaneous Boost in Neoadjuvant Radiotherapy for Rectal Cancer
NCT07209215	PHASE2	NOT_YET_RECRUITING	ctDNA-Informed Management of Early-Stage Rectal Cancer
NCT07292298	PHASE2	RECRUITING	Phase 2 Single-Arm Rectal Cancer Brachytherapy for Patients With Low-Lying Residual Adenocarcinoma After Total Neoadjuvant Therapy to Improve Organ Preservation Rates
NCT07407465	PHASE2	RECRUITING	Upfront Trastuzumab-Deruxtecan Plus Capecitabine and Bevacizumab for Patients With HER-2 Positive Metastatic Colorectal Cancer.
NCT07543848	PHASE2	NOT_YET_RECRUITING	A Prospective, Multicenter, Single-Arm Phase II Exploratory Study of Serplulimab Combined With Oncolytic Virus H101, Short-Course Radiotherapy, and XELOX Chemotherapy as Total Neoadjuvant Treatment for Locally Advanced (cT1-3N0M0) Rectal Cancer
NCT07595874	PHASE2	NOT_YET_RECRUITING	Neoadjuvant Botensilimab and Balstilimab for the Treatment of Advanced Resectable Colorectal Cancer NEST3
NCT00005818	PHASE1/PHASE2	COMPLETED	SU5416 and Irinotecan in Treating Patients With Advanced Colorectal Cancer

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
FLUOROURACIL	4	26
TIPIRACIL	4	8
LEUCOVORIN	4	7
TRIFLURIDINE	4	7
BEVACIZUMAB	4	3
ENCORAFENIB	4	3
OXALIPLATIN	4	3
REGORAFENIB	4	3
IPILIMUMAB	4	2
TUCATINIB	4	2
ABEMACICLIB	4	1
CAPECITABINE	4	1
CLOBETASOL PROPIONATE	4	1
ERLOTINIB	4	1
FLOXURIDINE	4	1
GEFITINIB	4	1
IRINOTECAN	4	1
LEVOLEUCOVORIN CALCIUM	4	1
MIDOSTAURIN	4	1
NINTEDANIB	4	1
PALBOCICLIB	4	1
PERTUZUMAB	4	1
TALIMOGENE LAHERPAREPVEC	4	1
VORINOSTAT	4	1
BALSTILIMAB	3	5
BOTENSILIMAB	3	5
VELIPARIB	3	2
ADEBRELIMAB	3	1
BAVITUXIMAB	3	1
ENILURACIL	3	1