GPER-1 and ERα36 in expanded ERα/PR/EGFR biomarker frameworks.
| Biomarker | Role | Evidence type | Tumor evidence | Subtype | Functional implication | Diagnostic value | Main references |
|---|---|---|---|---|---|---|---|
| ERα | Classical nuclear estrogen receptor | Primary experimental + clinical + genomic | Defines luminal tumors | Luminal A/B | Hormone-dependent transcriptional regulation | Core clinical marker | Clinical standard |
| PR | ERα downstream effector | Clinical + mechanistic | ER axis integrity | Luminal A/B | Functional ER signaling | Predicts endocrine response | Clinical standard |
| EGFR | RTK | Experimental + clinical | Aggressive tumors | TNBC/HER2 | MAPK/PI3K signaling | Aggressive marker | [10, 27, 79, 86, 106, 160] |
| GPER-1 | GPCR non-genomic | Experimental + pharmacology + translational | ~50–60% tumors | Luminal resistant/TNBC | Plasticity, resistance | ER-independent signaling | [22, 26, 28, 56, 66, 70, 85, 86, 90, 92, 93, 95–99, 101–103, 135, 160, 161] |
| ERα36 | Splice variant ESR1 | Experimental + translational | ~30–40% tumors | Luminal B/TNBC | EMT, resistance | Non-classical ER signaling | [10, 21, 25, 27, 104–106, 108–112, 114–117, 139] |
| GPER-1 +ERα36 | Crosstalk axis | Mechanistic integration | Not unified clinically | Luminal resistant/TNBC | Adaptive plasticity | Candidate axis | [24, 29, 54, 93, 121, 127] |
| Integration | Network signaling | Systems biology | Correlative datasets | All | MAPK/PI3K-transcription | Multi-marker support | [29, 79, 81, 97, 117, 143, 144, 162] |
| Limitation | Translational gap | Methodological | Limited validation | — | Context dependence | Needs clinical validation | [6, 163] |
LMC: Conceptualization, Resources, Formal analysis, Supervision, Funding acquisition, Validation, Investigation, Visualization, Writing—original draft, Writing—review & editing. YA: Formal analysis, Supervision, Validation, Investigation, Visualization, Writing—review & editing. RFT: Validation, Investigation, Writing—review & editing. J Spies: Supervision, Investigation, Writing—review & editing. SSM: Validation, Investigation, Writing—review & editing. MS: Investigation, Methodology, Writing—original draft. JC: Investigation, Methodology, Writing—original draft. JG: Investigation, Methodology, Writing—original draft. DM: Investigation, Methodology, Writing—original draft. J Soto: Investigation, Methodology, Writing—original draft. All authors read and approved the submitted version.
The authors declare that they have no conflicts of interest.
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This work was supported by ANID FONDECYT INICIACIÓN 11240855 (LMC), ANID FONDECYT INICIACIÓN 11230898 (RFT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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