Uterine cancer

Clinical / Scientific

Uterine cancers are mainly endometrial carcinomas; uterine sarcomas are biologically distinct mesenchymal tumours and should not inherit endometrial endocrine maps.

Core Biological Drivers

Endometrial PI3K/ER axis

Dominant carcinoma biology.

Sarcoma-specific fusions

Distinct mesenchymal drivers when present.

Key Pathways

PI3K/AKT

Scientific explanation

phosphorylates PIP2 to PIP3, recruiting . supports growth, survival, glucose uptake and mTORC1 input. Pathway activation is common via PIK3CA mutation, PTEN loss or -tyrosine- signalling.

Estrogen receptor

Scientific explanation

ERα (ESR1) drives a large fraction of breast cancers via genomic and non-genomic signalling. ESR1 mutations and growth-factor crosstalk contribute to endocrine resistance.

p53

Scientific explanation

TP53 encodes a stress-responsive factor controlling cell-cycle arrest, and metabolic adaptation. Loss or mutation is among the most common cancer events.

PD-1 / PD-L1

Scientific explanation

PD-1 on T cells engaging PD-L1/PD-L2 restrains cytotoxic function. Tumour or myeloid PD-L1 is a canonical adaptive immune-evasion axis.

Pathway Convergence

Target → pathway → downstream effect → biological consequence. Shared intersections are mechanistic maps, not protocols.

Growth-factor signalling

Ligand or mutation-driven RTK input feeds PI3K/AKT and mTORC1, supporting anabolic growth. This is a map of signalling, not a treatment protocol.

Receptor tyrosine kinase

↓

PI3K/AKT

↓

mTOR

↓

Protein synthesis / growth

Metabolic Vulnerabilities

Aerobic supports ATP, biomass and acidification even when oxygen is available. Extent varies by tumour and remains a vulnerability hypothesis rather than a uniform target.

Tumor Microenvironment

Disordered vasculature creates , HIF-1α stabilization, induction and immune-suppressive adenosine/lactate milieus.

Metastasis Module

, protease-mediated invasion, , circulating tumour-cell survival and organ-specific colonization form the metastatic cascade. Pre-metastatic niches and vascular permeability influence tropism.

Resistance Biology

Resistance can arise from drug efflux, secondary mutations, bypass RTK signalling, apoptotic threshold elevation, -mediated survival, metabolic adaptation and lineage plasticity.

Cancer Stemness

Wnt, Notch, Hedgehog, ALDH and CD44-associated programmes can mark stem-like fractions with quiescence and therapy tolerance. These markers are not interchangeable across tumour types.

Mechanism-Based Adjunctive Strategies

Compounds appear only where a mechanistic overlap exists for this cancer. Evidence tiers are not equivalent. Nothing here is a treatment recommendation.

Metformin

Clinical / Human EvidenceIn VivoIn VitroMechanistically Plausible

Target / Mechanism

Modest complex I inhibition raises AMP:ATP, activating and restraining hepatic and -linked anabolism. Direct antineoplastic efficacy is not established from that pharmacology alone.

Cancer relevance

activation and restraint provide a metabolic rationale in - and -linked tumours. Human data are mixed and do not establish metformin as cancer therapy.

Metabolic adjunctive research context. Convergence: AMPK, mTOR, Glycolysis.

Research Context

Hallmarks. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-674. https://doi.org/10.1016/j.cell.2011.02.013

This oncology atlas is educational. Pathway maps, adjunctive strategies, and compound listings describe mechanistic relevance. They do not establish clinical efficacy, do not recommend treatment, and are not a substitute for oncology care. Evidence tiers are not equivalent.