Rectal neoplasm

Summary

Rectal neoplasm (MONDO:0002165) is a cancer with 1 cohort gene (1 CIViC-evidence somatic driver; 1 ClinVar predisposition record) and 196 clinical trials. Top therapeutic interventions include indocyanine green acid form, dostarlimab, and epoetin alfa.

At a glance

• Classification: Cancer
• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 196

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	rectal neoplasm
Mondo ID	MONDO:0002165
MeSH	D012004
DOID	DOID:1984
NCIT	C3350
SNOMED CT	126847008
UMLS	C0034885
MedGen	11148
Anatomy (UBERON)	UBERON:0001052
Is cancer (heuristic)	yes

Also known as: neoplasm of rectum · neoplasm of the rectum · rectal neoplasm · rectal tumor · rectal tumour · rectum neoplasm (disease) · rectum tumor · rectum tumour · tumor of rectum · tumor of the rectum · tumour of rectum · tumour of the rectum

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › intestinal disorder › large intestine disorder › rectal disorder › rectal neoplasm

Related subtypes (5): anal fistula, ulcer of anus and rectum, anus disorder, rectal prolapse, polyp of rectum

Subtypes (4): anus neoplasm, rectal cancer, benign neoplasm of rectum, epithelial neoplasm of rectum

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

1 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
90623	NM_000251.3(MSH2):c.1313CTC[1] (p.Pro439del)	MSH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
MSH2			CIViC #3628

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MSH2	Orphanet:144	Lynch syndrome
MSH2	Orphanet:252202	Constitutional mismatch repair deficiency syndrome

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
MSH2	HGNC:7325	ENSG00000095002	P43246	DNA mismatch repair protein Msh2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MSH2	DNA mismatch repair protein Msh2	Component of the post-replicative DNA mismatch repair system (MMR).

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)
MSH2	Other/Unknown	no		DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N, DNA_mismatch_repair_MutS_core

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
oocyte	1
secondary oocyte	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MSH2	278	ubiquitous	marker	secondary oocyte, oocyte, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MSH2	4,537

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MSH2	P43246	30

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. 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
Defective Mismatch Repair Associated With MSH3	1	5710.0×	0.001	MSH2
Defective Mismatch Repair Associated With MSH6	1	5710.0×	0.001	MSH2
Defective Mismatch Repair Associated With MSH2	1	3806.7×	0.001	MSH2
Mismatch Repair	1	2855.0×	0.001	MSH2
Diseases of Mismatch Repair (MMR)	1	2855.0×	0.001	MSH2
Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)	1	815.7×	0.003	MSH2
Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)	1	815.7×	0.003	MSH2
Diseases of DNA repair	1	571.0×	0.003	MSH2
TP53 Regulates Transcription of DNA Repair Genes	1	181.3×	0.009	MSH2
DNA Repair	1	98.5×	0.015	MSH2
Transcriptional Regulation by TP53	1	62.1×	0.022	MSH2
RNA Polymerase II Transcription	1	22.5×	0.055	MSH2
Gene expression (Transcription)	1	17.8×	0.065	MSH2
Generic Transcription Pathway	1	15.1×	0.071	MSH2
Disease	1	13.1×	0.076	MSH2

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
somatic recombination of immunoglobulin genes involved in immune response	1	16852.0×	0.001	MSH2
somatic recombination of immunoglobulin gene segments	1	4213.0×	0.001	MSH2
B cell mediated immunity	1	4213.0×	0.001	MSH2
maintenance of DNA repeat elements	1	3370.4×	0.001	MSH2
mitotic recombination	1	2808.7×	0.001	MSH2
positive regulation of isotype switching to IgA isotypes	1	2808.7×	0.001	MSH2
response to UV-B	1	1872.4×	0.002	MSH2
DNA damage tolerance	1	1685.2×	0.002	MSH2
positive regulation of isotype switching to IgG isotypes	1	1532.0×	0.002	MSH2
oxidative phosphorylation	1	1404.3×	0.002	MSH2
negative regulation of DNA recombination	1	1123.5×	0.002	MSH2
somatic hypermutation of immunoglobulin genes	1	1053.2×	0.002	MSH2
mitotic intra-S DNA damage checkpoint signaling	1	936.2×	0.002	MSH2
response to X-ray	1	887.0×	0.002	MSH2
isotype switching	1	842.6×	0.002	MSH2
mismatch repair	1	648.1×	0.002	MSH2
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	1	495.6×	0.003	MSH2
germ cell development	1	455.5×	0.003	MSH2
determination of adult lifespan	1	432.1×	0.003	MSH2
B cell differentiation	1	218.9×	0.006	MSH2
double-strand break repair	1	203.0×	0.006	MSH2
male gonad development	1	156.0×	0.007	MSH2
negative regulation of neuron apoptotic process	1	110.9×	0.010	MSH2
in utero embryonic development	1	72.0×	0.014	MSH2
DNA repair	1	63.8×	0.016	MSH2

Therapeutics

Drugs indicated for this disease

0 approved, 9 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Bevacizumab	Phase 3 (in late-stage trials)
Capecitabine	Phase 3 (in late-stage trials)
Celecoxib	Phase 3 (in late-stage trials)
Fluorouracil	Phase 3 (in late-stage trials)
Irinotecan	Phase 3 (in late-stage trials)
Lanreotide	Phase 3 (in late-stage trials)
Oxaliplatin	Phase 3 (in late-stage trials)
Tegafur	Phase 3 (in late-stage trials)
Tislelizumab	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Cadonilimab, Curcumin, Dostarlimab, Durvalumab, Gimeracil, Nivolumab, Oteracil, Tecemotide, Trifluridine.

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
MSH2	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
MSH2	9	Binding:9

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).

Drug repurposing candidates

0 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

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	MSH2

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)
MSH2	9	—

Clinical trials & evidence

Clinical trials

Clinical trials: 196.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	125
PHASE2	42
PHASE3	11
PHASE1	7
PHASE4	5
PHASE1/PHASE2	4
PHASE2/PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00535652	PHASE4	COMPLETED	Concentration of Ertapenem in Colorectal Tissue
NCT01056913	PHASE4	COMPLETED	NITI CAR27 (ColonRing) Compression Anastomosis in Colorectal Surgery
NCT01912586	PHASE4	COMPLETED	Early Intervention for Erectile Dysfunction After Laparoscopic Resection for Rectal Cancer
NCT01975064	PHASE4	COMPLETED	Cancer and Anesthesia: Survival After Radical Surgery - a Comparison Between Propofol or Sevoflurane Anesthesia
NCT05068180	PHASE4	UNKNOWN	Low-dose Neuroleptanalgesia for Postoperative Delirium in Elderly Patients
NCT02505750	PHASE3	ACTIVE_NOT_RECRUITING	Safety of a Boost (CXB or EBRT) in Combination With Neoadjuvant Chemoradiotherapy for Early Rectal Adenocarcinoma
NCT06017583	PHASE3	RECRUITING	Neoadjuvant Chemotherapy With PD-1 Inhibitors Combined With SIB-IMRT in the Treatment of Locally Advanced Rectal Cancer
NCT00036400	PHASE3	COMPLETED	Study of the Efficacy and Safety of Epoetin Alfa Administered Weekly in Patients With Gastric or Rectal Cancers Undergoing a Treatment Plan of Preoperative Chemotherapy and Radiation Therapy, Followed by Surgery
NCT00056446	PHASE3	COMPLETED	Study of Oxaliplatin/5-FU/Leucovorin Plus Vatalanib Versus Oxaliplatin/5-FU/Leucovorin in Patients With Previously Treated Metastatic Colorectal Cancer
NCT00056459	PHASE3	COMPLETED	Study of Oxaliplatin/5-FU/Leucovorin Plus Vatalanib Versus Oxaliplatin/5-FU/Leucovorin in Patients With Metastatic Colorectal Cancer.
NCT00190541	PHASE3	COMPLETED	Mesorectal Excision (ME) Versus ME With Lateral Node Dissection for Stage II, III Lower Rectal Cancer (JCOG0212)
NCT00349076	PHASE3	COMPLETED	Neoadjuvant Chemoradiotherapy and Adjuvant Chemotherapy With 5-Fluorouracil and Oxaliplatin Versus 5-Fluorouracil Alone in Rectal Cancer
NCT00427375	PHASE3	COMPLETED	Local Excision in Downstaged Rectal Cancer
NCT01437514	PHASE2/PHASE3	TERMINATED	Effective Study of Preoperative Short-course Radiotherapy for the Advanced Resectable Rectal Cancer
NCT02288195	PHASE3	UNKNOWN	CONVERT: Neoadjuvant Chemotherapy Alone Versus Preoperative Chemoradiation for Locally Advanced Rectal Cancer Patients
NCT02598414	PHASE2/PHASE3	UNKNOWN	The Role of Indocyanine Green (ICG) Fluorescence Imaging on Anastomotic Leak in Robotic Colorectal Surgery
NCT02751606	PHASE3	UNKNOWN	Nano MRI on 7 Tesla in Rectal and Breast Cancer
NCT03415763	PHASE3	UNKNOWN	Adjuvant Chemotherapy in Patients With Clinical Stage III Rectal Cancer Undergoing Neoadjuvant Chemoradiotherapy
NCT03714490	PHASE2	RECRUITING	MRI Simulation-guided Boost in Short-course Preoperative Radiotherapy for Unresectable Rectal Cancer
NCT04755920	PHASE2	RECRUITING	SGM-101 in Colorectal Brain Metastases.
NCT05009069	PHASE2	ACTIVE_NOT_RECRUITING	A Study of Atezolizumab With or Without Tiragolumab Following Neoadjuvant Chemoradiotherapy in Participants With Locally Advanced Rectal Cancer
NCT05856305	PHASE2	ACTIVE_NOT_RECRUITING	SCRT in TNT With or Without Chlorophyllin
NCT06417476	PHASE2	ACTIVE_NOT_RECRUITING	Short-course Radiotherapy or Long-course Chemoradiation Followed by mFOLFOXIRI Consolidation Chemotherapy for Organ Preservation in Low Rectal 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
NCT00063427	PHASE2	COMPLETED	Study Evaluating MAC-321 in Colorectal Cancer
NCT00072748	PHASE2	COMPLETED	Study Evaluating EKB-569 in Advanced Colorectal Cancer
NCT00174616	PHASE2	COMPLETED	CORE: Capecitabine, Oxaliplatin, Radiotherapy and Excision
NCT00180960	PHASE2	TERMINATED	Treatment of a Cancerous Disease of the Peritoneum With Complete Cytoreductive Surgery and Intraperitoneal Chemohyperthermia
NCT00232453	PHASE2	COMPLETED	Preoperative Combined Radiation and Chemotherapy - Rectal Cancer
NCT00259363	PHASE1/PHASE2	TERMINATED	Oxaliplatin in Rectal Cancer
NCT00263029	PHASE2	COMPLETED	Preoperative Radiotherapy/ Oxaliplatin/ Capecitabine Treatment For Unresectable Locally-advanced Rectal Cancer
NCT00330915	PHASE2	COMPLETED	A Study of Pemetrexed and Folic Acid Given Before Surgery (Neoadjuvant Treatment) to Patients With Rectal Cancer.
NCT00403624	PHASE1/PHASE2	COMPLETED	Evaluation of the Neoadjuvant Treatment With Oxaliplatin -UFT- Radiotherapy in Rectal Cancer
NCT00421824	PHASE2	COMPLETED	Study of Neoadjuvant Chemotherapeutic Treatment (XELOX) Followed by Chemoradiotherapy (XELOX/RT) and Surgery Versus Chemoradiotherapy Followed by Surgery and Chemotherapy in Patients With High Risk Rectal Cancer
NCT00506623	PHASE2	UNKNOWN	Preoperative Chemoradiotherapy With Capecitabine Plus Irinotecan in Rectal Cancer
NCT00506844	PHASE2	UNKNOWN	Preoperative Chemoradiotherapy With Cetuximab in Rectal Cancer
NCT00557713	PHASE2	UNKNOWN	XELOX+Bevacizumab Followed by Capecitabine+Bevacizumab+Radiotherapy as Neoadjuvant Treatment of Locally Advanced Rectal Adenocarcinoma
NCT00832299	PHASE2	TERMINATED	Neo-Adjuvant FOLFOX for Rectal Carcinoma
NCT01060007	PHASE2	COMPLETED	Five Fractions of Radiotherapy Followed by Full Dose FOLFOX Chemotherapy as Preoperative Treatment for Rectal Cancer
NCT01273051	PHASE2	COMPLETED	Transanal Endoscopic Microsurgery (TEM) After Radiochemotherapy for Rectal Cancer

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
INDOCYANINE GREEN ACID FORM	4	2
DOSTARLIMAB	4	1
EPOETIN ALFA	4	1
ERTAPENEM	4	1
LEVOLEUCOVORIN	4	1
NIRAPARIB	4	1
OXALIPLATIN	4	1
PROPOFOL	4	1
SEVOFLURANE	4	1
TISLELIZUMAB	4	1
VATALANIB	3	4
FERUMOXTRAN-10	3	1
MINERAL OIL	3	1
TIRAGOLUMAB	3	1
CHLOROPHYLLIN COPPER COMPLEX	2	1
DALOTUZUMAB	2	1
MILATAXEL	2	1
PELITINIB	2	1
SODIUM FORMATE	0	1