# Endometrial cancer (KEGG map)

Source: https://onco.cc/pathways/endometrial-cancer-signalling/  
OnCo record `endometrial-cancer-signalling` (Pathway). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

KEGG's endometrial cancer map shows oestrogen-related type I tumours with PTEN loss, KRAS and beta-catenin mutations and faulty mismatch repair, and type II tumours with TP53 mutation and HER2 amplification. Immunotherapy for mismatch-repair-deficient tumours and HER2-directed therapy follow directly from this split.

## Summary

The KEGG endometrial cancer map (hsa05213) separates the two classical types. Type I (endometrioid) carcinoma follows unopposed oestrogen exposure and endometrial hyperplasia and shows loss of PTEN, the most frequent event, releasing PI3K to AKT signalling (with PIK3CA and PIK3R1 mutations adding to it), activating KRAS mutations feeding RAF to MEK to ERK, stabilising CTNNB1 (beta-catenin) mutations that escape the APC/AXIN/GSK3B destruction complex and drive TCF/LEF and MYC transcription, and defects in DNA mismatch repair (MLH1 promoter methylation, or germline Lynch syndrome mutations) that produce microsatellite instability. Type II (serous and other non-endometrioid) carcinoma arises in atrophic endometrium, lacks hormone receptors and shows TP53 mutation, aneuploidy and ERBB2 (HER2) amplification with downstream EGFR/ERBB2 to RAS and PI3K signalling. Crosbie et al., Lancet, 2022 (doi:10.1016/S0140-6736(22)00323-3) update this into the four molecular classes now used clinically: POLE ultramutated, mismatch repair deficient, p53 abnormal, and no specific molecular profile, which predict outcome and guide adjuvant therapy.

What drugs do about it: PD-1 antibodies (dostarlimab, pembrolizumab, durvalumab) added to carboplatin and paclitaxel are now first-line for advanced or recurrent disease, with the largest benefit in mismatch-repair-deficient tumours; pembrolizumab with lenvatinib treats mismatch-repair-proficient tumours after chemotherapy; trastuzumab and trastuzumab deruxtecan target HER2-positive serous tumours; and hormonal therapy (progestins, aromatase inhibitors such as letrozole, sometimes with the mTOR inhibitor everolimus) exploits the oestrogen dependence of low-grade type I disease.

## Fields

- Kind: Pathway
- Last checked: 2026-09-10
- Also known as: KEGG hsa05213; Endometrial cancer
- Analogy: Two different break-ins. In type I the alarm system (PTEN, mismatch repair) is disabled and oestrogen keeps the doors open; the intruders leave so many fingerprints (mutations) that the immune police can recognise them once PD-1 antibodies unmask them. In type II a single master key (TP53 loss, HER2 amplification) does the damage, so HER2-targeted drugs are the tool.
- Interventions: PD-1 antibodies dostarlimab, pembrolizumab or durvalumab with carboplatin and paclitaxel for advanced or recurrent disease, especially mismatch-repair-deficient tumours; Pembrolizumab plus lenvatinib for mismatch-repair-proficient disease after platinum chemotherapy; HER2-directed therapy (trastuzumab with chemotherapy, trastuzumab deruxtecan) for HER2-positive serous carcinoma; Hormonal therapy (progestins, letrozole, with or without everolimus) for low-grade oestrogen-receptor-positive disease; Molecular classification (POLE, mismatch repair, p53) to de-escalate or intensify adjuvant treatment after surgery

## Sources

- KEGG map hsa05213: https://www.kegg.jp/pathway/hsa05213
- Review: Endometrial cancer (Lancet 2022): https://doi.org/10.1016/S0140-6736(22)00323-3

## Connected records

- pathways: [Mismatch repair & microsatellite instability](https://onco.cc/pathways/mismatch-repair-msi/), [Oestrogen receptor signalling](https://onco.cc/pathways/er-signaling/), [p53 / RB / cell-cycle checkpoint](https://onco.cc/pathways/p53-cell-cycle/), [PD-1 / PD-L1 immune checkpoint & T-cell activation](https://onco.cc/pathways/pd1-checkpoint/), [PI3K / AKT / mTOR](https://onco.cc/pathways/pi3k-akt-mtor/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/), [Wnt / β-catenin](https://onco.cc/pathways/wnt/)
- cancers: [Endometrial cancer](https://onco.cc/cancers/endometrial/)
- targets: [CTNNB1](https://onco.cc/targets/ctnnb1/), [Estrogen receptor (ERα)](https://onco.cc/targets/estrogen-receptor/), [HER2](https://onco.cc/targets/her2/), [KRAS](https://onco.cc/targets/kras/), [MLH1](https://onco.cc/targets/mlh1/), [PIK3CA / PI3K-alpha](https://onco.cc/targets/pik3ca/), [TP53](https://onco.cc/targets/tp53/)
- drugs: [Dostarlimab](https://onco.cc/drugs/dostarlimab/), [Durvalumab](https://onco.cc/drugs/durvalumab/), [Everolimus](https://onco.cc/drugs/everolimus/), [Lenvatinib](https://onco.cc/drugs/lenvatinib/), [Letrozole (and other aromatase inhibitors)](https://onco.cc/drugs/letrozole/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Trastuzumab](https://onco.cc/drugs/trastuzumab/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/)
- key papers: [Endometrial cancer](https://onco.cc/key-papers/paper-crosbie-lancet/)

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