DeCure for Estrogen-receptor negative breast cancer
DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for estrogen-receptor negative breast cancer — screening already-approved drugs against its 28-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleEstrogen-receptor negative breast cancer maps to a 28-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
approvedSunitinibApproved drug
Structures already discussed alongside estrogen-receptor negative breast cancer in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
KIT kinase domain — Sunitinib has a real, experimentally solved structure in complex with this target (PDB 3G0E, 1.6 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet b49drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3G0E · 1.6 Å · ligand Sunitinib (B49). Experimental structure, not a prediction.
What the evidence adds up to
Estrogen receptor-negative breast cancer carries a worse prognosis than receptor-positive disease. A retrospective cohort study in Ethiopia of 368 patients, with equal numbers of receptor-negative and receptor-positive cases, found that the incidence density rate of mortality for receptor-negative patients was 10.47 per 1,000 person-years (95% CI 8.19–13.37), compared to 5.48 per 1,000 person-years (95% CI 3.94–7.64) for receptor-positive patients. After full adjustment for confounders, the mortality hazard was 32% higher in the receptor-negative group (HR 1.32; 95% CI 1.08–2.91). A 1987 analysis of 501 breast cancer cases reported that recurrences were more frequent in estrogen receptor-negative patients, and that better responses to anti-estrogen therapy occurred in receptor-positive patients.
Oral selective estrogen receptor degraders (SERDs) are pure estrogen receptor antagonists under investigation for estrogen receptor-positive breast cancer, with five drugs in published or ongoing trials: elacestrant, camizestrant, giredestrant, imlunestrant, and amcenestrant. These agents are described as reasonably well-tolerated with low discontinuation rates, but the review summarising them does not address receptor-negative disease. Anti-hormone therapy, including selective estrogen receptor modulators, is used only for hormone-dependent breast tumours. A 2017 editorial notes that breast cancer recurrences, especially in estrogen receptor-negative disease, occur within the first five years after diagnosis, and that many patients experience significant treatment-related adverse events without clinical benefit.
No drug specifically tested in estrogen receptor-negative breast cancer appears in these abstracts. The available data confirm that receptor-negative status carries a higher mortality risk and that existing endocrine therapies are not applicable to this subtype. What remains missing is any dedicated clinical trial of a drug or combination regimen for receptor-negative disease, adequate funding for such trials, and a strategy for patient stratification that might identify the subset of receptor-negative patients who could respond to a targeted approach.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cancer Cell International · 2014 · 23 citations · open access
Inhibition of proliferation and migration of luminal and claudin-low breast cancer cells by PDGFR inhibitors
AbstractBACKGROUND: Platelet-derived growth factors (PDGFs) bind to two receptors, PDGFRα and PDGFRβ to mediate cell proliferation, migration and survival. Although epithelial cells typically do not express high levels of PDGFRs, their expression has been reported to increase in breast cancer cells that have undergone epithelial to mesenchymal transition. METHODS: PDGFR signaling was inhibited using Sunitinib malate, Imatinib mesylate or Regorafenib in murine and human luminal-like and claudin-low mammary tumor cell lines or Masitinib in only the human cell lines. A scratch wound assay was used to assess tumor cell migration while immunofluorescence for phosphorylated histone H3 or cleaved caspase 3 was used to determine tumor cell proliferation and apoptosis, respectively. RESULTS: Sunitinib and Regorafenib, but not Imatinib, were capable of significantly inhibiting the migration of both murine and human luminal-like and claudin-low breast cancer cells while Masitinib inhibited migration in both human breast cancer cell lines. Sunitinib but not Regorafenib or Imatinib also significantly suppressed tumor cell proliferation in all four cell lines tested while Masitinib had no significant effect on human breast cancer cell proliferation. None of the PDGFR inhibitors consistently regulated mammary tumor cell apoptosis. CONCLUSION: Sunitinib, Regorafenib and Masitinib may prove clinically useful in inhibiting breast cancer cell migration and metastasis while only Sunitinib (and possibly Regorafenib in some breast cancer subtypes) is effective at inhibiting both migration and proliferation of breast cancer cells.
Journal of the National Comprehensive Cancer Network · 2005 · 23 citations · open access
Aromatase Inhibitors in Postmenopausal Breast Cancer Patients
AbstractAromatase inhibitors (AIs) have greatly enriched the treatment of hormone receptor-positive breast cancer in postmenopausal patients. Before the introduction of the well-tolerated third-generation AIs, tamoxifen was the mainstay of endocrine therapy for hormone receptor-positive breast cancer. Many clinical trials have shown the superiority of AIs compared with tamoxifen in adjuvant breast cancer treatment, as well as their benefit in metastatic breast cancer. NCCN guidelines recommendations for their use are based on the evidence provided by these clinical trials. This discussion reviews the evidence supporting the current guidelines for use of AI therapy in the treatment of hormone receptor-positive postmenopausal breast cancer patients.
Annual Review of Medicine · 2025 · 15 citations · open access
New Oral Selective Estrogen Receptor Degraders Redefine Management of Estrogen Receptor–Positive Breast Cancer
AbstractOral selective estrogen receptor degraders (SERDs) are pure estrogen receptor antagonists that have the potential to overcome common resistance mechanisms to endocrine therapy in estrogen receptor-positive breast cancer. There are currently five oral SERDs in published and ongoing clinical trials-elacestrant, camizestrant, giredestrant, imlunestrant, and amcenestrant-with more in development. They offer a reasonably well-tolerated oral therapy option with low discontinuation rates in studies. This review summarizes the currently available literature on this new class of drugs.
Modern approaches to the treatment of breast cancer.
AbstractBreast cancer is the most common cause of cancer death in women in this country. Until recently, the traditional treatment has been radical surgery with or without radiation therapy for patients with primary breast cancer, and palliative endocrine therapy followed by chemotherapy for patients with advanced disease. These treatments have met with limited effectiveness in terms of eradicating the disease. Studies in the past decade have given cause for optimism for breast cancer patients. Adjuvant systemic therapy after local treatment appears promising for certain subsets of patients with primary breast cancer. The development of estrogen receptor assays has markedly changed our approach to the disease and improved patient care. Estrogen receptor is an important prognostic factor and is useful in planning appropriate therapy for patients with primary breast cancer as well as those with advanced disease. Further research is urgently needed to improve the dismal survival of certain women with this common malignancy.
Breast Cancer Targets and Therapy · 2022 · 12 citations · open access
The Effect of Estrogen Receptor Status on Survival in Breast Cancer Patients in Ethiopia. Retrospective Cohort Study
AbstractBackground: There is wide global variance in survival from breast cancer, both in developed and developing country. However, the effect of estrogen receptor status has not been widely evaluated in Ethiopia where the incidence of breast cancer is rapidly increasing. Hence, the current study aimed to determine the effect of estrogen receptor status on the overall survival of breast cancer patients who were treated at Black Lion Specialized Hospital, Ethiopia. Methods: In this institution-based retrospective cohort study a total of 368 study participants were included with a one-to-one ratio of estrogen receptor negative to estrogen receptor positive. The main outcome of interest for this study was death due to breast cancer. The authors compared the women with estrogen receptor-positive and estrogen receptor-negative breast cancer for overall survival rate using log rank test. The incidence density rate of mortality was calculated for each exposed and non-exposed variable. The effect of estrogen receptor status on breast cancer mortality was estimated using the Cox proportional hazards model. Results: The incidence density rate of mortality among breast cancer patients for estrogen receptor positive were found to be 5.48 (95% CI=3.94-7.64) per 1,000 person years observation; while for estrogen negative receptor status the mortality rate was found to be 10.47 (95% CI=8.19-13.37) per 1,000 person years observation. In the Cox regression analysis after ful adjustments for confounder variables, the mortality event risk was 32% higher among estrogen receptor negative (HR=1.32; 95% CI=1.08-2.91) as compared to estrogen receptor positive breast cancer patients. Conclusion: We have found that the incidence density rate of mortality among breast cancer patients was significantly higher in the estrogen receptor negative groups. Therefore, clinicians should give careful attention to the impact of estrogen receptor negative status on the overall outcome of clients.
American Society for Clinical Laboratory Science · 2012 · 0 citations · open access
Anti-hormones: Mechanism and Use in Treatment of Breast Cancer
AbstractBreast cancer is the second-leading cause of cancer-related death in women. Recently, new drugs are being developed based on the molecular mechanisms of receptors, tumor suppressor genes, monoclonal antibodies, tumor markers and antihormone therapy. Anti-hormone therapy is used in the treatment of hormone-dependent breast tumors. Among the anti-hormone therapies, a substantial amount of research has been focused on the development of the ideal selective estrogen receptor modulator to treat metastatic breast tumors and to prevent breast cancer in high risk women.
International Journal of Gynecology & Obstetrics · 1987 · 0 citations
Estrogen receptors in breast cancer ‐ therapeutic response to the treatment of recurrences
AbstractThe authors analyze estrogen receptors in 501 cases of breast cancer and the therapeutic response achieved with treatment of patients who relapsed. The method utilized to determine the presence of estrogen receptor was cytosol protein-counting and Dextran coated charcoal (DCC) saturation analysis. Patients were treated with chemotherapy when the primary tumor was estrogen-receptor negative. If receptor was present, anti-estrogen drug (Tamoxifen) was added. Patients previously treated with the anti-estrogen presented a better response to anti-estrogen therapy and a lower recurrence rate. Recurrences were more frequent in estrogen receptor negative cases and better responses to treatment were found in estrogen receptor positive ones.
Journal of Laboratory and Precision Medicine · 2017 · 0 citations · open access
Editorial on “Gene expression signatures in circulating tumor cells correlate with response to therapy in metastatic breast cancer”
AbstractBreast cancer recurrences, especially in patients with estrogen receptor (ER)-negative disease occur within the first 5 years after diagnosis (1). Several therapeutic options are available for the treatment of metastatic breast cancer, such as surgery, radiotherapy, hormone treatment, chemotherapy as well as targeted therapies (2). However, it would be very important to predict which patients will benefit from each treatment, since several patients experience significant treatment-related adverse events without any clinical benefit.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
