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Receptor Mechanisms and Signaling / Cancer, Stress, Anesthesia, and Immune Response / Pharmacological Receptor Mechanisms and Effects · Journal article
Kinases and Phosphatases · September 8, 2026
Raises a question worth testing. It does not answer one.
This is a narrative review summarizing preclinical mechanistic evidence linking TMEM97/sigma-2 receptor expression to endocrine therapy resistance in hormone receptor-positive breast cancer through mTOR signaling and cholesterol metabolism pathways. The authors acknowledge that evidence remains preclinical and call for further investigation, indicating this work represents early-stage hypothesis generation rather than clinical evidence.
Journal article. Hormone receptor-positive breast cancer cells (preclinical models).
TMEM97/σ2R is highly expressed in hormone receptor-positive breast cancer High TMEM97/σ2R expression is associated with endocrine resistance via enhanced mTOR signaling TMEM97/σ2R elevates estrogen receptor activities conferring increased resistance to endocrine therapy
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
This work identifies a potential therapeutic target but is at an early mechanistic stage; clinicians should not alter practice based on this review. Further investigation, including clinical studies, is required before TMEM97/sigma-2 receptor inhibition can be considered for endocrine resistance.
This is a mechanistic review summarizing preclinical evidence linking TMEM97/sigma-2 receptor to endocrine resistance pathways; the source explicitly states evidence remains preclinical and further investigation is needed.
This work identifies a potential therapeutic target but is at an early mechanistic stage; clinicians should not alter practice based on this review. Further investigation, including clinical studies, is required before TMEM97/sigma-2 receptor inhibition can be considered for endocrine resistance.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
What is missing. This record has no reported figures. That is a gap in the analysis, not a judgement about the study.
Breast cancer remains one of the most common cancers in women, in which the majority of cases exhibit a hormone receptor-positive subtype. Although several treatment options are available for patients with this subtype, first-line therapies mainly rely on the patient’s sensitivity to endocrine therapy. Therapy resistance, which frequently develops over the treatment course, remains a key obstacle for clinical intervention. Efforts are currently underway to elucidate additional therapeutic targets to restore endocrine therapy sensitivity and treat hormone receptor-positive breast cancer. Here, we summarize work surrounding the sigma-2 receptor (σ2R) and its potential role in endocrine therapy resistance pathways, including PI3K-mTOR signaling and cholesterol metabolism. Although σ2R was pharmacologically characterized decades ago, its molecular identity remained elusive until 2017, when transmembrane protein 97 (TMEM97) was established as the sigma-2 receptor. TMEM97/σ2R is highly expressed in hormone receptor-positive breast cancer and its RNA expression levels are associated with endocrine resistance. High expression of TMEM97/σ2R elevates estrogen receptor activities and confers breast cancer cells with increased resistance to endocrine therapy via enhanced mTOR signaling. Given the role of TMEM97 in cholesterol homeostasis, understanding the connections between TMEM97/σ2R, breast cancer, and cholesterol regulation may reveal new pathways to aid in the development of targeted therapies. Evidence remains preclinical, and further investigation is needed to confirm hypothesized pathways involving TMEM97/σ2R in breast cancer endocrine resistance.
Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.