DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for HER2 Positive Breast Carcinoma — screening already-approved drugs against its 41-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHER2 Positive Breast Carcinoma maps to a 41-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 her2 positive 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
neurotrophic receptor tyrosine kinase 2 (NTRK2) — NTRK2 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 4-methoxybenzyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4AT5 · 1.71 Å · ligand 5-{3-methoxy-4-[(4-methoxybenzyl)oxy]benzyl}pyrimidine-2,4-diamine (MUJ). Experimental structure, not a prediction.
What the evidence adds up to
About one third of patients with HER2-positive breast cancer eventually relapse after initial treatment. A non-interventional study of 216 patients re-treated with trastuzumab (Herceptin) in the first-line advanced setting reported a median progression-free survival of 12.7 months (95% CI 10.5–14.8) and a median overall survival of 31.6 months (95% CI 28.8–38.4) from the time of recurrence diagnosis. Patients with visceral metastases had the worst prognosis. No new cardiac safety concerns were observed. The same study noted that the median time to relapse after initial therapy was 36.5 months.
A review of the field in 2020 stated that four new drugs had been approved for HER2-positive breast cancer within the preceding 18 months, and that ongoing trials were exploring immunotherapy and CDK4/6 inhibitors in the advanced setting, as well as extending treatment to patients with HER2-low breast cancer. Earlier reviews noted that continuing trastuzumab with chemotherapy or another HER2-targeted agent showed benefit in trastuzumab-resistant disease, and that targeting VEGF, mTOR, and PI3 kinase pathways alongside HER2 might enhance efficacy.
A single-institution study of 100 patients in southern Tunisia found that pT stage, pN stage, capsular effraction, vascular invasion, perineural invasion, and nipple involvement were independent prognostic factors for overall survival and disease-free survival in patients without distant metastasis at diagnosis. For patients with synchronous metastasis, no independent pathologic prognostic factor for survival was identified. The authors concluded that HER2-positive disease is a heterogeneous entity and that molecular predictors of benefit and resistance to anti-HER2 therapy are needed.
What is still missing is prospective trial data on which patients benefit from re-treatment versus switching to a different HER2-targeted agent, validated biomarkers to stratify the heterogeneous HER2-positive population, and randomised evidence for combining HER2 blockade with immunotherapy or CDK4/6 inhibitors. The non-interventional design of the re-treatment study limits confidence in its effectiveness estimates, and no cost-effectiveness data are available for the newer approved drugs in resource-limited settings.
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.
Anticancer Research · 2020 · 5 citations · open access
Resumption of Trastuzumab in Patients With Disease Recurrence After (Neo-) Adjuvant Anti-HER2-therapy in Patients With HER2-positive Breast Cancer
AbstractBACKGROUND/AIM: HER2-positive breast cancers eventually relapse in about one third of patients. Is anti-HER2-directed therapy with Herceptin® (trastuzumab) effective in re-treatment? Between 2008 and 2018, 216 patients with recurrent HER2-positive breast cancer (BC) were re-treated with Herceptin (HER) during first-line therapy. This study assessed the effectiveness and tolerability of re-treatment with HER. PATIENTS AND METHODS: After approval from Ethical committee, the NIS was conducted according to German Drug Act. Re-treatment with HER was documented at routine visits starting with a basic observational period of maximum 12 months and a follow-up period of maximum additional four years. RESULTS: HER2-positive BC relapsed after a median of 36.5 months (mos). Patients were re-treated with HER +/- chemotherapy +/- endocrine therapy. HER-containing regimens resulted in median progression-free survival (mPFS) of 12.7 (95%CI=10.5-14.8) mos and overall survival (OS-2) of 31.6 mos (95%CI=28.8-38.4) since recurrence diagnosis. Differentiation of recurrence types (local, visceral, non-visceral) unfolded worst prognosis for patients with visceral metastases. Cardiac monitoring within this non-interventional study (NIS) did not result in new safety concerns. CONCLUSION: Re-therapy with HER in the first-line setting of advanced HER2-positive breast cancer is effective and without unexpected or intensified adverse events.
Current Opinion in Obstetrics & Gynecology · 2020 · 3 citations
Frontiers in HER2-positive breast cancer in 2020
AbstractPURPOSE OF REVIEW: The field of HER2-positive breast cancer has seen tremendous advances in the last 2 years with largest number of new drugs in decades. The present review aims to summarize the cutting-edge research of the past 2 years and future directions. RECENT FINDINGS: This review will go over four new drugs, three of which have gained FDA approval within the past 18 months, in the treatment of HER2-positive breast cancer. We will go over early and mature clinical data on these therapeutics and ongoing clinical trials further exploring their role in the treatment of patients with advanced HER2-positive breast cancer and HER2 low breast cancer. Will also discuss ongoing trials using immunotherapy and CDK4/6 inhibitors in the advanced HER2-positive setting. SUMMARY: : The therapies described in this review have quickly become standard of care for patients with HER2-positive breast cancer. Furthermore, they have the potential to change the landscape of breast cancer therapy further to include even patients with HER2 low breast cancer.
The prognostic significance of pathological features in Her-2 overexpressing breast carcinomas: A single institution experience in southern Tunisia
AbstractBACKGROUND: Breast cancer is the most frequent malignant neoplasm affecting Tunisian women. It represents 25 to 35% of all female cancers. There is no published study about the features of Her-2 overexpressing breast carcinomas in North African women. OBJECTIVE: The aim of this study is to assess the prognostic significance of pathological features in a cohort of a Her-2 overexpressing breast carcinoma originating from the region of south Tunisia. METHODS: This study investigated a series of 100 patients followed from January 2006 to December 2011 for a Her-2 positive invasive breast carcinoma. Pathological features included in this study were: histological type, histological grade, tumor size, vascular invasion, perineural invasion, mitotic index, lymph nodes stage, positive lymph node capsular effraction, inflammatory infiltrates, nipple involvement and hormone receptors status. RESULTS: Multivariate analysis showed that pT stage, pN stage, capsular effraction, vascular invasion, perineural invasion and Nipple involvement were independent prognostic factors for overall survival and disease free survival in patients free from distant metastasis at diagnosis. For patients with synchronous metastasis, there is no independent pathologic prognostic factor for survival. CONCLUSIONS: Our study demonstrates that pathological features are important prognostic factors for non metastatic Her-2 overexpressing breast carcinomas. This supports the idea that HER2-positive disease is a heterogeneous entity. We believe that these findings reinforce the need to identify molecular predictors of benefit and resistance to anti-Her-2 based therapies.
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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