DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for lymphatic system cancer — 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 moduleLymphatic system cancer 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
approvedSunitinibApproved drug
Structures already discussed alongside lymphatic system 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
The 2016 review on lymphangiogenesis and angiogenesis in tumour metastasis states that both blood and lymphatic vessels are routes for cancer cell spread, and that lymphangiogenesis and angiogenesis are associated with poor prognosis. It mentions lymphatic vessel density, blood vessel density, interstitial fluid pressure, tumour hypoxia, and regional lymph node metastasis as factors influencing tumour cell motility and clinical outcome. No drug, intervention, or quantitative outcome data are provided. A second 2016 review discusses the lymphatic system’s role in fluid homeostasis and immune cell trafficking, and states that increasing knowledge of its molecular control will lead to new therapies for lymphatic dysfunction, including cancer and lymphedema. Again, no specific treatment or numerical results are given.
The 2014 review on lymphatic targeted drug delivery for tumour metastasis notes that lymphatic metastatic tumours develop rapidly, that surgical resection, radiotherapy, and chemotherapy have low effectiveness, and that lymph node metastasis may predict endpoint events. It describes the exploration of lymphatic targeted drug delivery systems to improve specificity of anticancer drugs to tumour cells in lymph nodes, but provides no clinical trial data, response rates, or survival figures. The 2020 review on cellular origins of the lymphatic endothelium states that lymphangiogenesis during cancer progression can have both positive and negative effects: tumour-associated lymphatic vessels correlate with metastatic dissemination and poor prognosis, yet functional lymphatics may benefit anti-tumour immunity and immunotherapy delivery. It notes controversy over cellular sources of tumour lymphatics, but offers no drug or patient outcome data.
Across these four abstracts, no drug is named, no treatment is tested in patients, and no concrete numbers for survival or response rates are reported. The evidence is entirely mechanistic and descriptive. What is still missing is any clinical trial testing a specific agent against lymphatic system cancer, any patient stratification strategy, and the funding to move from molecular description to interventional studies.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cellular Oncology · 2016 · 311 citations · open access
The role of lymphangiogenesis and angiogenesis in tumor metastasis
AbstractBACKGROUND: Metastasis is the main cause of mortality in cancer patients. Two major routes of cancer cell spread are currently being recognized: dissemination via blood vessels (hematogenous spread) and dissemination via the lymphatic system (lymphogenous spread). Here, our current knowledge on the role of both blood and lymphatic vessels in cancer cell metastasis is summarized. In addition, I will discuss why cancer cells select one or both of the two routes to disseminate and I will provide a short description of the passive and active models of intravasation. Finally, lymphatic vessel density (LVD), blood vessel density (BVD), interstitial fluid pressure (IFP) and tumor hypoxia, as well as regional lymph node metastasis and the recently discovered primo vascular system (PVS) will be highlighted as important factors influencing tumor cell motility and spread and, ultimately, clinical outcome. CONCLUSIONS: Lymphangiogenesis and angiogenesis are important phenomena involved in the spread of cancer cells and they are associated with a poor prognosis. It is anticipated that new discoveries and advancing knowledge on these phenomena will allow an improvement in the treatment of cancer patients.
Annual Review of Biomedical Engineering · 2016 · 246 citations
The Lymphatic System in Disease Processes and Cancer Progression
AbstractAdvances in our understanding of the structure and function of the lymphatic system have made it possible to identify its role in a variety of disease processes. Because it is involved not only in fluid homeostasis but also in immune cell trafficking, the lymphatic system can mediate and ultimately alter immune responses. Our rapidly increasing knowledge of the molecular control of the lymphatic system will inevitably lead to new and effective therapies for patients with lymphatic dysfunction. In this review, we discuss the molecular and physiological control of lymphatic vessel function and explore how the lymphatic system contributes to many disease processes, including cancer and lymphedema.
Recent advances in lymphatic targeted drug delivery system for tumor metastasis.
AbstractThe lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tumor cells may even transfer to other organs to form other types of tumors. Clinically, lymphatic metastatic tumors develop rapidly. Given the limitations of surgical resection and the low effectiveness of radiotherapy and chemotherapy, the treatment of lymphatic metastatic tumors remains a great challenge. Lymph node metastasis may lead to the further spread of tumors and may be predictive of the endpoint event. Under these circumstances, novel and effective lymphatic targeted drug delivery systems have been explored to improve the specificity of anticancer drugs to tumor cells in lymph nodes. In this review, we summarize the principles of lymphatic targeted drug delivery and discuss recent advances in the development of lymphatic targeted carriers.
Frontiers in Physiology · 2020 · 30 citations · open access
Cellular Origins of the Lymphatic Endothelium: Implications for Cancer Lymphangiogenesis
AbstractThe lymphatic system plays important roles in physiological and pathological conditions. During cancer progression in particular, lymphangiogenesis can exert both positive and negative effects. While the formation of tumor associated lymphatic vessels correlates with metastatic dissemination, increased severity and poor patient prognosis, the presence of functional lymphatics is regarded as beneficial for anti-tumor immunity and cancer immunotherapy delivery. Therefore, a profound understanding of the cellular origins of tumor lymphatics and the molecular mechanisms controlling their formation is required in order to improve current strategies to control malignant spread. Data accumulated over the last decades have led to a controversy regarding the cellular sources of tumor-associated lymphatic vessels and the putative contribution of non-endothelial cells to this process. Although it is widely accepted that lymphatic endothelial cells (LECs) arise mainly from pre-existing lymphatic vessels, additional contribution from bone marrow-derived cells, myeloid precursors and terminally differentiated macrophages, has also been claimed. Here, we review recent findings describing new origins of LECs during embryonic development and discuss their relevance to cancer lymphangiogenesis.
Efficacy of Sunitinib in Patients With Favorable and Intermediate Risk Metastatic Renal Cell Carcinoma – Lithuanian National Cancer Institute Experience
AbstractBACKGROUND/AIM: According to the European Society for Medical Oncology (ESMO) and National Comprehensive Cancer Network (NCCN) recommendations, sunitinib is one of the recommended regimens for favorable and intermediate-risk metastatic renal cell carcinoma (mRCC) patients. The objective of this study was to evaluate sunitinib efficacy as a first-line treatment for mRCC patients with favorable/intermediate prognostic risk in a real-world setting. PATIENTS AND METHODS: Patients diagnosed with mRCC and confirmed as appropriate candidates for the first-line systemic treatment were included in this retrospective study. The prognostic risk was evaluated according to the model of the International Metastatic RCC Database Consortium (IMDC). RESULTS: Patients received sunitinib as a first-line treatment. A total of 94 patients were enrolled from 2019 to the 2020and 67 of them were included in the detailed analysis. Median progression-free survival (PFS) was 23.4 (95%CI=17.3-29.5), and median overall survival (OS) was 66 months (95%CI=44.9-87.1). The age over 60 years was a significant negative predictor for PFS and OS. Regarding the IMDC model for disease risk prediction, the number of two risk factors in the intermediate risk group was a significant predictor for a shorter response to the first-line therapy. CONCLUSION: Sunitinib is an effective tyrosine kinase inhibitor, which can be used as a first-line treatment in favorable/intermediate-risk groups of patients with mRCC, especially in countries where novel systemic treatment modalities are not yet available.
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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