DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for HER2 negative breast carcinoma — screening already-approved drugs against its 13-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHER2 negative breast carcinoma maps to a 13-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
approvedFulvestrantApproved drug
Structures already discussed alongside her2 negative breast carcinoma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Crystal structure of human soluble epoxide hydrolase — Fulvestrant has a real, experimentally solved structure in complex with this target (PDB 4J03, 2.92 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 fvsdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4J03 · 2.92 Å · ligand Fulvestrant (FVS). Experimental structure, not a prediction.
What the evidence adds up to
The 2010 review covers HER2-positive breast cancer only, not HER2-negative disease. It states that trastuzumab-resistant tumours may benefit from continuing trastuzumab with chemotherapy or another HER2-targeted agent, and that adding inhibitors of VEGF, mTOR, or PI3 kinase pathways may improve efficacy. No survival or response numbers are given for any regimen. The review does not address HER2-negative breast carcinoma.
A 2015 commentary notes that targeting HER2 is validated for HER2-positive cancers but that the HER receptor family may have roles beyond HER2 amplification. It calls for biomarkers to identify such cancers. No clinical data, sample sizes, or outcomes are reported.
A 2022 article summarises the emerging concept of HER2-low breast cancer, defined as HER2 expression 1+ or 2+ by immunohistochemistry with negative FISH. It states that first results with new-generation antibody-drug conjugates are promising in this group, which currently falls within luminal and triple-negative categories. The article does not report specific response rates, survival figures, or sample sizes from any trial. It predicts that ongoing studies may allow anti-HER2 therapy in a wider group, including HER2-low patients, and that the current binary classification of HER2 status may need revision to include an intermediate group.
What is still missing: large randomised trials with mature survival data for HER2-low patients treated with new-generation conjugates, validated cut-offs for low HER2 expression, and prospective stratification of HER2-negative tumours by HER2 level rather than by the current binary system. Funding for such trials and for biomarker development remains limited.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Obstetrics & Gynecology · 2010 · 110 citations
Human epidermal growth factor receptor-2-positive breast cancer: current management of early, advanced, and recurrent disease
AbstractPURPOSE OF REVIEW: This review describes the current treatment of human epidermal growth factor receptor-2 (HER2)-positive breast cancer with a focus on recently reported clinical trials.Treatment of resistant disease and central nervous system metastases will be reviewed as will new agents that are being developed to target HER2-amplified breast cancers. RECENT FINDINGS: Recent studies evaluating trastuzumab-resistant breast cancer have shown a benefit of continuing trastuzumab with chemotherapy or with another HER2-targeted agent.Targeting the vascular endothelial growth factor, mammalian target of rapamycin, and PI3 kinase pathways in addition to HER2 may enhance efficacy compared with individual agents. Several novel anti-HER2 compounds are being evaluated with promising early data. SUMMARY: HER2-positive breast cancer has traditionally been associated with poor prognosis.However, treatment with HER2-targeted therapies has changed the natural history of this disease. Greater success depends on elucidating mechanisms of resistance and exploring new methods of blocking signal transduction via HER2 and related pathways.
Oncology in Clinical Practice · 2022 · 1 citations · open access
HER2-low — the new subtype of breast cancer?
AbstractIn the recent years, intensive research has been carried out on the use of targeted therapy against HER2 receptor in patients with the currently recognized HER2-negative breast cancer. The first results of studies with new generation conjugates are promising in the group of patients with HER2-low breast cancer (HER2 expression 1+ or 2+ in immunohistochemistry with negative FISH). This article summarizes the available data on this potentially new group of breast cancer that is now part of the luminal and triple-negative breast cancers. Data on clinical features of HER2-low cancer are discussed, as well as the results of clinical trials with anti-HER2 therapy in these patients are summarized. The efficacy of the new generation conjugates was recorded. The results of ongoing studies with these drugs may allow to use anti-HER2 therapy in a wider group of patients, including ones with HER2-low cancers. The new concept of “HER2-low” breast cancer will force a revision of the current division of breast cancer depending on HER2 expression into only two groups, introducing an intermediate group with low HER2 expression.
Breast Cancer Management · 2017 · 0 citations · open access
Fulvestrant in Breast Cancer: Also a Good Option in Triple-Positive Breast Cancer
AbstractFulvestrant is indicated in the treatment of locally advanced or metastatic breast cancer in postmenopausal women with hormone receptor-positive breast cancer as second line at the present time, after first line hormone therapy. We present here a case report of a 47-year-old woman diagnosed with infiltrating ductal carcinoma left breast cancer in 1998, stage II, luminal B HER2-positive and a liver and ganglionar relapse 3 years later. After radical treatment, fulvestrant was indicated. She has been 10 years with this treatment, with an excellent tolerance and without showing progression until now.
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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