DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for bilateral breast carcinoma — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleBilateral breast carcinoma maps to a 1-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 bilateral 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
ATM serine/threonine kinase (ATM) — ATM 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 anpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8OXQ · 2.5 Å · ligand PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER (ANP). Experimental structure, not a prediction.
What the evidence adds up to
In a 1997 study of 498 postoperatively irradiated breast cancer patients (T1-4,N0-3,M0), 36 developed bilateral carcinoma. The 10-year overall survival was 54% for unilateral disease and 56% for bilateral disease. Metastasis incidence was 24.2% versus 38.8%, and local failure occurred in 11% of unilateral patients versus 19.4% for the first tumour and 11.1% for the second in bilateral patients. The authors concluded that bilateral occurrence had no significant impact on survival, though local failures and metastases appeared more frequent.
A 1999 study compared 60 bilateral breast cancer patients (44 metachronous, 16 synchronous) with 1,080 unilateral patients, all treated with breast conservation therapy (lumpectomy, axillary dissection, radiotherapy). Median tumour size was 1.4 cm for bilateral and 1.5 cm for unilateral; median total dose to the tumour bed was 60 Gy for both groups. With median follow-up of 45–52 months, 5-year overall survival was 76% for synchronous, 78% for metachronous, and 87% for unilateral patients (p = 0.32). Five-year failure-free survival was 79%, 73%, and 85% respectively (p = 0.28). Local failure rate was 3% in both bilateral and unilateral groups. A significant difference in family history of breast cancer was found between unilateral and bilateral patients (p = 0.028), but family history did not affect outcome.
A 2024 study used copy number profiling and whole exome sequencing on a subset of bilateral breast cancers that were clonally related, identifying a somatic mutation, SIVA-D160N, acquired in what the authors describe as breast-to-breast metastasis. In vitro, over-expression of SIVA-D160N promoted migration and invasion of human MDA-MB-231 breast cancer cells and invasion and anchorage-independent growth of mouse 4T1 cells. In vivo, tail vein injection of 231 cells over-expressing SIVA-D160N showed enhanced distant spread on IVIS imaging; orthotopic mammary fat pad injection of 4T1 cells over-expressing SIVA-D160N in syngeneic Balb/c mice increased primary tumour growth and liver metastasis.
What is still missing: prospective trials comparing treatment strategies specifically for bilateral breast cancer, validation of SIVA-D160N as a clinically useful biomarker or therapeutic target in human patients, and any drug or intervention that modulates SIVA function in a clinical setting.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
OncoTargets and Therapy · 2018 · 39 citations · open access
The effects of naloxone on human breast cancer progression: in vitro and in vivo studies on MDA.MB231 cells
AbstractBACKGROUND: Naloxone is viewed as a specific competitive opioid antagonist acting at the level of opioid receptors (μ, δ, and κ) with blended agonist-adversary or agonist action. The role of naloxone in tumor cell growth has been poorly studied in human cancer cell lines. MATERIALS AND METHODS: In the present study, we report findings from in vitro and in vivo experiments performed to evaluate the effects of naloxone on human breast cancer cell growth and progression. In vitro assays were conducted on estrogen receptor-negative human breast carcinoma cells, MDA.MB231, treated with naloxone at different concentrations (10-100 μM). In vivo experiments were performed on a mouse model of human triple-negative breast cancer generated by using MDA.MB231 injected subcutaneously in mice. Naloxone was daily intraperitoneally injected in mice at 0.357 mg/kg for 2 weeks and at 0.714 mg/kg for the next 2 weeks. Microvessels formation was detected by fluorescein isothiocyanate-dextran (100 μL) injected into the tail vein of mice and confirmed by immunohistochemistry with CD31 on mice tumor sections. RESULTS: In vitro tests showed that the cell proliferation of MDA.MB231 was inhibited by naloxone in a dose-dependent manner, whereas the cell death was increased. In vivo studies demonstrated that tumors of mice treated with naloxone were significantly smaller than those observed in the control groups, as long as naloxone was administered. Finally, naloxone was not able to impair the microvessel formation in tumors of treated mice. CONCLUSION: Our data showed, for the first time, that naloxone reduced breast cancer progression without affecting angiogenesis.
American Journal of Clinical Oncology · 1997 · 37 citations
Bilateral Breast Carcinoma Versus Unilateral Disease
AbstractIn literature data, an uncertainty exists whether occurrence of bilateral breast cancer decreases the survival probability of affected patients. Therefore, we analyzed the medical records of 498 postoperatively irradiated (1977-1982) female breast cancer patients (T1-4,N0-3,M0). In the follow-up time, in 36 patients a bilateral breast carcinoma treated by surgery with or without radiotherapy was found. The 10-year overall survival rates were 54% in patients who had unilateral disease, compared with 56% in bilateral carcinoma patients, respectively. The incidence of metastasis did not differ between both groups: 24.2% versus 38.8%. Eleven percent of unilateral cancers recurred; in the other group, local failure of the first and second tumor was observed in 19.4% and 11.1%, respectively. We conclude that the occurrence of bilateral breast cancer has no significant impact on survival, although the development of local failures and metastases seems to be more frequent. The therapeutic strategy in bilateral carcinoma should resemble the treatment procedure in unilaterally affected patients.
Efficacy of Breast Conservation Therapy in Early Stage Bilateral Breast Cancer
AbstractThe purpose of this study was to evaluate the outcome of patients with bilateral breast cancer as compared to unilateral breast cancer treated with breast conservation therapy. Sixty patients with bilateral breast cancer (BBC) and 1,080 unilateral breast cancer (UBC) patients treated with breast conservation therapy from 1977 to 1994 were analyzed for outcome. Of the 60 bilateral patients, 44 were metachronous bilateral breast cancer patients (MBBC) and 16 were synchronous bilateral breast cancer patients (SBBC). The majority of patients received lumpectomy, axillary node dissection, and localized radiation therapy. Median tumor size was 1.4 cm for BBC and 1.5 cm for UBC patients. Median total dose to the tumor bed was 60 Gy for both unilateral and bilateral patients. Of the 44 MBBC patients, 14 received breast conservation for both the first and second lesions, while 30 received breast conservation for only the second metachronous lesion. Thus 58 lesions in 44 patients were treated with breast conservation therapy. Of the SBBC patients, 13 of 16 patients received breast-conserving therapy for both breasts, while 3 received a mastectomy for the second synchronous primary. Median follow-up was 50 months for SBBC patients, 45 months for MBBC patients, and 52 months for UBC patients. Local control and survival were analyzed in patients with SBBC, MBBC, and UBC. The interval to development of local recurrence and survival were calculated from the time of development of the second breast lesion in patients with MBBC. No differences were found for survival and failure-free survival in patients with SBBC, MBBC, or UBC. Five-year overall survival by lifetable analysis was 76% for SBBC, 78% for MBBC, and 87% for UBC patients (p = 0.32 by log-rank analysis). The 5-year failure-free survival was 79% for SBBC, 73% for MBBC, and 85% for UBC patients (p = 0.28 by log-rank analysis). No significant differences were seen for median age, tumor size, pathologic node status, tamoxifen use, chemotherapy use, or median total radiation dose for SBBC, MBBC, or UBC patients. A significant difference was found in the incidence of family history of breast cancer in patients with unilateral versus bilateral breast cancer (p = 0.028 by chi-square analysis). However, there was no difference in outcome of patients by family history of breast cancer. The local control was identical in both BBC and UBC patients, with a local failure rate of 3%. Therefore, breast conservation therapy in local-regional, early stage breast cancer is a rational and efficacious treatment modality for patients with SBBC, MBBC, and UBC.
Breast Cancer Online · 2005 · 9 citations · open access
Synchronous bilateral invasive breast cancer
AbstractSynchronous bilateral invasive breast cancer is a rare event. The etiology of bilateral breast cancer is uncertain, but most evidence supports independent tumors and not metastasis spread from one of the primary tumors. The prognosis of bilateral breast cancer was once thought to be poor, but recent data has suggested a similar survival for bilateral breast cancers as compared to unilateral disease.
Abstract<div> Metastasis is the most dreaded outcome after a breast cancer diagnosis, and little is known regarding what triggers or promotes breast cancer to spread distally, or how to prevent or eradicate metastasis effectively. Bilateral breast cancers are an uncommon form of breast cancers. In our study, a percentage of bilateral breast cancers were clonally related based on copy number variation profiling. Whole exome sequencing and comparative sequence analysis revealed that a limited number of somatic mutations were acquired in this “breast-to-breast” metastasis that might promote breast cancer distant spread. One somatic mutation acquired was <i>SIVA-D160N</i> that displayed pro-metastatic phenotypes <i>in vivo</i> and <i>in vitro</i>. Over-expression of <i>SIVA-D160N</i> promoted migration and invasion of human MB-MDA-231 breast cancer cells <i>in vitro</i>, consistent with a dominant negative interfering function. When introduced via tail vein injection, 231 cells over-expressing <i>SIVA-D160N</i> displayed enhanced distant spread on IVIS imaging. Over-expression of <i>SIVA-D160N</i> promoted invasion and anchorage independent growth of mouse 4T1 breast cancer cells <i>in vitro</i>. When introduced orthotopically via mammary fat pad injection in syngeneic Balb/c mice, over-expression of <i>SIVA-D160N</i> in 4T1 cells increased orthotopically implanted mammary gland tumor growth as well as liver metastasis. Clonally related bilateral breast cancers represented a novel system to investigate metastasis and revealed a role of <i>SIVA-D160N</i> in breast cancer metastasis. Further characterization and understanding of SIVA function, and that of its interacting proteins, may elucidate mechanisms of breast cancer metastasis, providing clinically useful biomarkers and therapeutic targets. </div>
Abstract<div> Metastasis is the most dreaded outcome after a breast cancer diagnosis, and little is known regarding what triggers or promotes breast cancer to spread distally, or how to prevent or eradicate metastasis effectively. Bilateral breast cancers are an uncommon form of breast cancers. In our study, a percentage of bilateral breast cancers were clonally related based on copy number variation profiling. Whole exome sequencing and comparative sequence analysis revealed that a limited number of somatic mutations were acquired in this “breast-to-breast” metastasis that might promote breast cancer distant spread. One somatic mutation acquired was <i>SIVA-D160N</i> that displayed pro-metastatic phenotypes <i>in vivo</i> and <i>in vitro</i>. Over-expression of <i>SIVA-D160N</i> promoted migration and invasion of human MB-MDA-231 breast cancer cells <i>in vitro</i>, consistent with a dominant negative interfering function. When introduced via tail vein injection, 231 cells over-expressing <i>SIVA-D160N</i> displayed enhanced distant spread on IVIS imaging. Over-expression of <i>SIVA-D160N</i> promoted invasion and anchorage independent growth of mouse 4T1 breast cancer cells <i>in vitro</i>. When introduced orthotopically via mammary fat pad injection in syngeneic Balb/c mice, over-expression of <i>SIVA-D160N</i> in 4T1 cells increased orthotopically implanted mammary gland tumor growth as well as liver metastasis. Clonally related bilateral breast cancers represented a novel system to investigate metastasis and revealed a role of <i>SIVA-D160N</i> in breast cancer metastasis. Further characterization and understanding of SIVA function, and that of its interacting proteins, may elucidate mechanisms of breast cancer metastasis, providing clinically useful biomarkers and therapeutic targets. </div>
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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