DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for luminal B breast carcinoma — screening already-approved drugs against its 45-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleLuminal B breast carcinoma maps to a 45-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
No approved-drug candidate for luminal b breast carcinoma is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
AKT serine/threonine kinase 1 (AKT1) — AKT1 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet propanoylaminodrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7NH5 · 1.9 Å · ligand ~{N}-methyl-6-[4-[[4-[2-oxidanylidene-6-(propanoylamino)-3~{H}-benzimidazol-1-yl]piperidin-1-yl]methyl]phenyl]-5-phenyl-pyridine-3-carboxamide (UC8). Experimental structure, not a prediction.
What the evidence adds up to
Luminal B breast cancer is defined by gene expression profiling as one of four intrinsic subtypes, distinct from luminal A, HER2-positive, and basal-like. In a 2009 study of 357 tumours classified by gene expression, 19% were luminal B. A Ki67 index cut point of 13.25% best distinguished luminal B from luminal A. In an independent cohort of 2847 hormone receptor-positive tumours, 33% were classified as luminal B using HER2 status and Ki67 index. Among women who received tamoxifen as their sole adjuvant systemic therapy, 10-year breast cancer-specific survival was 64% for luminal B, compared with 79% for luminal A and 57% for luminal-HER2 subtypes. Luminal B and luminal-HER2-positive cancers were statistically significantly associated with poor recurrence-free and disease-specific survival across all adjuvant treatment categories.
Luminal B tumours express oestrogen receptor but show higher proliferation, lower progesterone receptor expression, higher grade, and predicted poor response to hormone therapy. They do not show corresponding expression of oestrogen-regulated genes and may rely on alternative growth pathways. At the molecular level, luminal B cancers are distinct from luminal A in gene expression, gene copy number, somatic mutation, and DNA methylation, and are genetically and genomically altered to a greater extent. Candidate pathways that might be targeted include those involving HER2, EGFR, and PI3K/Akt/mTor. Several biological pathways have been identified as possible contributors to poor outcomes, and novel agents targeting these pathways are being developed, but no specific drug is established for luminal B in these abstracts.
Retrospective series and early-phase clinical trials have shown promising signs of activity and a favourable toxicity profile for the combination of metronomic chemotherapy with endocrine therapy in luminal breast cancer, but this warrants further investigation. A 2022 literature review states that modern treatment depends on immunohistochemical characteristics, genetic profile, age, histology, and stage, and that adjuvant hormone therapy reduces recurrence and mortality. In initial stages, combined surgical and hormonal treatment has higher survival rates than radical mastectomy alone. Local radiotherapy may induce immunotherapeutic effects.
What is still missing are prospective randomised trials that stratify patients specifically by luminal B subtype, validated biomarkers to predict which patients will benefit from targeted agents or metronomic schedules, and funding to move candidate pathway inhibitors (such as those targeting PI3K/Akt/mTor or growth factor receptors) through clinical testing in this defined population.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
JNCI Journal of the National Cancer Institute · 2009 · 2230 citations · open access
Ki67 Index, HER2 Status, and Prognosis of Patients With Luminal B Breast Cancer
AbstractBACKGROUND: Gene expression profiling of breast cancer has identified two biologically distinct estrogen receptor (ER)-positive subtypes of breast cancer: luminal A and luminal B. Luminal B tumors have higher proliferation and poorer prognosis than luminal A tumors. In this study, we developed a clinically practical immunohistochemistry assay to distinguish luminal B from luminal A tumors and investigated its ability to separate tumors according to breast cancer recurrence-free and disease-specific survival. METHODS: Tumors from a cohort of 357 patients with invasive breast carcinomas were subtyped by gene expression profile. Hormone receptor status, HER2 status, and the Ki67 index (percentage of Ki67-positive cancer nuclei) were determined immunohistochemically. Receiver operating characteristic curves were used to determine the Ki67 cut point to distinguish luminal B from luminal A tumors. The prognostic value of the immunohistochemical assignment for breast cancer recurrence-free and disease-specific survival was investigated with an independent tissue microarray series of 4046 breast cancers by use of Kaplan-Meier curves and multivariable Cox regression. RESULTS: Gene expression profiling classified 101 (28%) of the 357 tumors as luminal A and 69 (19%) as luminal B. The best Ki67 index cut point to distinguish luminal B from luminal A tumors was 13.25%. In an independent cohort of 4046 patients with breast cancer, 2847 had hormone receptor-positive tumors. When HER2 immunohistochemistry and the Ki67 index were used to subtype these 2847 tumors, we classified 1530 (59%, 95% confidence interval [CI] = 57% to 61%) as luminal A, 846 (33%, 95% CI = 31% to 34%) as luminal B, and 222 (9%, 95% CI = 7% to 10%) as luminal-HER2 positive. Luminal B and luminal-HER2-positive breast cancers were statistically significantly associated with poor breast cancer recurrence-free and disease-specific survival in all adjuvant systemic treatment categories. Of particular relevance are women who received tamoxifen as their sole adjuvant systemic therapy, among whom the 10-year breast cancer-specific survival was 79% (95% CI = 76% to 83%) for luminal A, 64% (95% CI = 59% to 70%) for luminal B, and 57% (95% CI = 47% to 69%) for luminal-HER2 subtypes. CONCLUSION: Expression of ER, progesterone receptor, and HER2 proteins and the Ki67 index appear to distinguish luminal A from luminal B breast cancer subtypes.
Breast Cancer Research · 2011 · 249 citations · open access
Luminal-B breast cancer and novel therapeutic targets
AbstractGene expression profiling has led to a new molecular classification of breast cancer characterized by four intrinsic subtypes: basal-like, HER2-positive, luminal A, and luminal B. Despite expressing estrogen receptor, the luminal-B subtype confers increased risk of early relapse with endocrine therapy compared with the luminal-A subtype. Although luminal-B definitions vary, the hallmark appears to be increased expression of proliferation-related genes. Several biological pathways are identified as possible contributors to the poor outcomes, and novel agents targeting these pathways are being developed with aims to improve survival. We review the definition of luminal-B breast cancer, its pathological and clinical features, and potential targets for treatment.
AbstractMolecular profiling studies have found that estrogen receptor-positive (ER+) human breast cancers are comprised of at least two distinct diseases with differing biologies. With the advent of DNA microarrays, global gene expression patterns were used to define the luminal A and luminal B subtypes of ER+ breast cancer, with luminal B cancers showing a more aggressive phenotype including substantially worse outcomes in patients. The luminal B subtype designation could be considered a surrogate for those ER+ tumors having low progesterone receptors, high proliferation, high grade, and predicted poor response to hormone therapy. While they express estrogen receptors, luminal B cancers do not show a corresponding expression of estrogen-regulated genes, and may therefore rely upon alternative pathways for growth. At the molecular level, luminal B cancers appear dramatically distinct from luminal A cancers, at the levels of gene expression, gene copy, somatic mutation, and DNA methylation; luminal B cancers are also genetically and genomically altered to a greater extent than luminal A cancers. While, in the clinical setting, luminal B is typically regarded as an ER+, hormone-sensitive disease, more research is needed into how to better treat it. Comprehensive profiling initiatives, such as The Cancer Genome Atlas, have recently provided us a catalog of mutated or copy altered genes, from which new therapeutic targets could potentially be mined. Candidate pathways that might be targeted in luminal B include those involving growth factor receptors, including HER2 and EGFR, as well as PI3K/Akt/mTor.
Expert Review of Anticancer Therapy · 2020 · 10 citations
Metronomic chemotherapy combined with endocrine therapy: are we challenging some dogmas?
AbstractINTRODUCTION: Metronomic chemotherapy exerts its effects via inhibition of angiogenesis, immune modulation of the tumoral stroma, induction of senescence and apoptosis of tumor cells. Due to its favorable toxicity profile and its oral administration, metronomic chemotherapy arises as a promising alternative to be combined with endocrine therapy for the treatment of patients with luminal breast cancer. AREAS COVERED: The present manuscript reviews the rationale supporting the combination of metronomic chemotherapy and endocrine therapy, discussing the studies that evaluated this regimen in the treatment of early-stage and metastatic breast cancer patients. Finally, we conclude by providing an expert opinion on the current role and perspectives for the combination of metronomic chemotherapy and endocrine therapy in the management of patients with luminal breast cancer. EXPERT OPINION: Retrospective series and early-phase clinical trials have shown promising signs of activity and a favorable toxicity profile with this regimen, which warrants further investigation as a treatment option for luminal breast cancer patients.
Zenodo (CERN European Organization for Nuclear Research) · 2022 · 0 citations · open access
RECENT TREATMENT TACTICS FOR THE PATIENT WITH LUMINAL BREAST CANCER. LITERARY REVIEW
Abstract<strong>Objectives. </strong>The aim of the study was to analyze evidence based data from existing sources, regarding the treatment tactics for the patient with luminal breast cancer. <strong>Material and methods. </strong>Google Scholar and PubMed, Central PubMed and international medical literature search engines were used to find evidence based data regarding the treatment tactics for the patient with luminal breast cancer. The following keywords were used for search: “breast cancer”, “luminal subtype”, “estrogen receptor”, “radical mastectomy”. <strong>Results. </strong>There were identified 51 scientific publications that reflect current evidence regarding the treatment tactics for the patient with luminal breast cancer. <strong>Conclusions. </strong>The modern treatment of breast cancer is complex and depends on the immunohistochemical characteristics, genetic profile, age, histological results and stage of the tumor. Most breast cancers are diagnosed at an early stage and are hormone positive receptors, therefore adjuvant treatment with hormonotherapy significantly reduces the rate of recurrence and mortality. In the initial stages, combined treatment (surgical and hormonal) has higher survival rates compared to radical mastectomies. According to the latest studies, local radiotherapy can induce immunotherapeutic effects in patients with breast cancer.
DOAJ (DOAJ: Directory of Open Access Journals) · 2022 · 0 citations · open access
RECENT TREATMENT TACTICS FOR THE PATIENT WITH LUMINAL BREAST CANCER. LITERARY REVIEW
Abstract<strong>Objectives. </strong>The aim of the study was to analyze evidence based data from existing sources, regarding the treatment tactics for the patient with luminal breast cancer. <strong>Material and methods. </strong>Google Scholar and PubMed, Central PubMed and international medical literature search engines were used to find evidence based data regarding the treatment tactics for the patient with luminal breast cancer. The following keywords were used for search: “breast cancer”, “luminal subtype”, “estrogen receptor”, “radical mastectomy”. <strong>Results. </strong>There were identified 51 scientific publications that reflect current evidence regarding the treatment tactics for the patient with luminal breast cancer. <strong>Conclusions. </strong>The modern treatment of breast cancer is complex and depends on the immunohistochemical characteristics, genetic profile, age, histological results and stage of the tumor. Most breast cancers are diagnosed at an early stage and are hormone positive receptors, therefore adjuvant treatment with hormonotherapy significantly reduces the rate of recurrence and mortality. In the initial stages, combined treatment (surgical and hormonal) has higher survival rates compared to radical mastectomies. According to the latest studies, local radiotherapy can induce immunotherapeutic effects in patients with breast cancer.
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.
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