DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for liver cancer — screening already-approved drugs against its 42-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleLiver cancer maps to a 42-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 drugapprovedSorafenibApproved drugapprovedVandetanibApproved drug
Structures already discussed alongside liver 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
Most liver cancer patients in China are diagnosed at middle or advanced stage and cannot have surgery, which remains the only treatment that can achieve long-term survival or cure. Conversion therapy aims to turn unresectable tumours into resectable ones using local treatments such as TACE, TARE or HAIC, systemic targeted therapy alone or with immunotherapy, or combinations of these. After conversion, maintenance treatment is chosen based on the outcome to maximise survival benefit. Surgery is also considered an alternative for some intermediate and advanced stage patients, and experts are now combining surgical and drug approaches for early and intermediate disease.
In a 2010 mouse hepatocyte transplantation assay, the oncogenes c-myc and transforming growth factor alpha increased hepatocyte growth rate under growth-permissive conditions, but no single oncogene could drive growth in quiescent liver. Only the combination of transforming growth factor alpha and T-antigen was sufficient for cell-autonomous growth even in a non-permissive environment. T-antigen’s main carcinogenic effect was to increase transformation frequency. The authors propose this system can prioritise targets for therapeutic intervention by quantifying the biological role of candidate genetic changes.
Despite decades of research, liver cancer remains a rapidly fatal disease, and pharmacological therapies do not significantly improve prognosis for patients with unresectable cancer. Several signal transduction inhibitors with clinical efficacy and generally favourable toxicity have entered practice, but the need to identify new druggable targets persists. Ongoing work examines deregulation of the methionine cycle, alterations in mRNA splicing, post-translational modifications such as sumoylation and neddylation, and the role of branched-chain amino acids and serum Clusterin. A neddylation inhibitor is being considered therapeutically, and inhibitors of Clusterin expression are also under consideration for targeted therapy.
What is still missing are large-scale clinical trials that test combined inhibition of different signalling pathways, methods to correlate molecular deregulation with treatment response, and reliable patient stratification to select who might benefit from personalised therapy. The evidence for conversion therapy and maintenance regimens comes largely from Chinese practice and lacks randomised controlled data from diverse populations. The preclinical work remains confined to mouse models and has not yet produced validated biomarkers or drugs that change the poor prognosis of advanced liver cancer.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
BioScience Trends · 2021 · 183 citations · open access
Conversion therapy and maintenance therapy for primary hepatocellular carcinoma
AbstractThe preferred treatment for hepatocellular carcinoma (HCC) is surgery, which is the only way to achieve long-term survival and even a cure. However, the vast majority of patients with liver cancer in China are already in the middle to advanced stage of the disease and no longer have the opportunity to undergo surgery. The goal of conversion therapy is to transform unresectable advanced liver cancer or potentially resectable liver cancer into resectable cancer, so it has become a topic of interest in the treatment of advanced liver cancer. Common modalities of conversion therapy are: local treatment (TACE, TARE, or HAIC), systemic treatment (targeted therapy alone or combined with immunotherapy), and a therapeutic alliance (TACE combined with radiation therapy, TACE combined with targeted therapy, HAIC combined with targeted therapy, or HAIC combined with targeted therapy and immunotherapy). The plan for maintenance treatment after conversion therapy is determined based on the outcome of conversion therapy to obtain the best survival benefit for patients.
Quantifying growth and transformation frequency of oncogene‐expressing mouse hepatocytes in vivo†
AbstractUNLABELLED: Gene changes can affect cancer cells in many ways, but changes that increase disease severity--by allowing cells to proliferate when they should be quiescent, by enhancing their rate of growth under growth permissive conditions, or by increasing the risk that they will accumulate additional carcinogenic alterations--must be identified so that strategies to counter their effects can be developed. We describe a novel in vivo assay system based on hepatocyte transplantation that permits us to accomplish this objective for genetically modified hepatocytes. We find that the oncogenes c-myc and transforming growth factor alpha, but not simian virus 40 T-antigen, increase the rate of hepatocyte growth under growth permissive conditions. However, no single oncogene can induce hepatocyte growth in quiescent liver. In contrast, at least one oncogene combination, transforming growth factor alpha/T-antigen, was sufficient to direct cell autonomous growth even in this nonpermissive environment. Furthermore, we could quantify risk for progression to neoplasia associated with oncogene expression; increased transformation frequency was the principal carcinogenic effect of T-antigen. CONCLUSION: This system identifies biological mechanistic role(s) in carcinogenesis for candidate genetic changes implicated in development of human liver cancer. The quantitative and comparative evaluation of gene effects on liver cancer allows us to prioritize targets for therapeutic intervention.
[Precise combination of systemic therapy and hepatic surgery].
AbstractIn China, the mortality rate of primary liver cancer ranks third among malignant tumors, so it is an imperative health issue. Surgery has always been an ideal treatment for early liver cancer, and an alternative treatment for some intermediate and advanced stage liver cancers. In recent years, significant progress has been made in the treatment of liver cancer, and relevant experts have begun to combine existing treatment methods into the early and intermediate-stage to explore drug treatment methods. Here, we will discuss the surgical and drug treatment issues, as well as the combination of the both, and their impact on future liver cancer treatment models.
Translational Gastroenterology and Hepatology · 2018 · 0 citations · open access
New insights on liver carcinogenesis
AbstractThe incidence of human liver cancer is particularly elevated in sub-Saharan Africa and far eastern Asia, where the infections by hepatitis B and hepatitis C are endemic and food may be contaminated by aflatoxin B1.The incidence is also rising in Europe and United States, due to the elevated occurrence of hepatitis C virus infection, cirrhosis related to type II diabetes, and non-alcoholic steatohepatitis.Liver cancer still is a rapid fatal disease and the therapies with pharmacological agents or alternative strategies do not improve significantly the prognosis of patients with unresectable cancer.This emphasizes the need to investigate the molecular mechanisms responsible for liver cancer development to identify new targets for early diagnosis, chemoprevention, and treatment.In the last decades a body of work examined the deregulation of signal transduction pathways involved in the pathogenesis of liver cancer, in the attempt to identify novel diagnostic and prognostic markers, and targets for cancer treatment.Several investigators have analyzed the role of aberrant activation of cellular signaling pathways during hepatocarcinogenesis. Novel therapeutic targets were discovered by genome-wide analysis of gene expression leading to the identification of gene signatures of different cancer types.The rationale for the molecular therapy of cancer is the knowledge that oncogenes and oncosuppressor genes encode proteins that are mutated or deregulated forms of key components of regulatory pathways.Thus, in order to kill cancerous cells, leaving unaffected normal cells, huge amount of work attempted to develop anticancer drugs targeting signal transduction mechanisms of liver cells, and a number of signal inhibitors with clinical efficacy and generally favorable toxicity have been introduced into clinical practice.This special issue of Translational Gastroenterology and Hepatology contains selected review articles on the progress, in the basic and clinical science, of the knowledge on the pathogenesis and molecular therapy of liver cancer, and looks forward to future developments.Several important and timely investigations on various aspects of hepatocarcinogenesis are currently published.Different of these studies are considered in the present special issue.The deregulation of the methionine cycle in liver cancer is presently the object of research by different scientists.The analysis of the role of this deregulation in cancer progression is crucial for its possible links to cancer prognosis and therapy.Other relevant pathogenetic aspects of liver cancer include alterations of mRNA splicing and a spectrum of post-translational modifications of proteins concerning numerous critical signaling events.Indeed, alterations of sumoylation and phosphorylation may influence protein stability and transcription, and protein-protein interactions thus affecting numerous signaling pathways involved in tumor cell growth.Also, the post-translational modifications of proteins may represent a therapeutic approach for liver cancer.Alterations of protein neddylation in HCC have been associated with poor prognosis and a neddylation inhibitor is presently considered for its therapeutic effect.Branched-chain aminoacids (BCAA) are also the object of recent interesting studies due to their involvement in different bioprocesses including protein metabolism, gene expression, insulin resistance and hepatocytes proliferation.Their importance in liver carcinogenesis is also shown by the observation that the administration of BCAA-rich medicines has positive results in patients with cirrhosis.Studies on the relationships between the level of serum Clusterin and the prognosis of liver cancer revealed that Clusterin could contribute to liver cancer cell migration, epithelial-mesenchymal transition and formation of metastases.The inhibitors of serum Clusterin expression are presently considered for targeted therapy of liver cancer.Other valuable new approaches to the treatment of liver cancer are included in the present special issue.They consider targeting of particular signaling pathways, stimulation of tumor cells autophagy and targeting of these cells and their permissive microenvironment simultaneously.This special issue of the Translational Gastroenterology and Hepatology has not been conceived to propose a comprehensive overview of all recent advances in the pathogenesis and personalized molecular therapy of liver tumors.The aim of this issue is to focus on some of the major topics, treated by experts in the field, dedicated to liver cancer prevention and therapy.The lesson for future developments is the need to expand our knowledge on the deregulation of cellular signaling pathways, involved in liver cancer development and progression, in order to identify new ''druggable" targets.Furthermore, the effects of the combined inhibition of different signaling pathways, the correlations between molecular deregulation and response to therapy, and the methods to select the patients that could be successfully treated by personalized therapy are major themes Preface New insights on liver carcinogenesis
A Multinational, Randomized, Open-Label, Phase 3 Study Of Sunitinib Malate Versus Sorafenib In Patients With Advanced Hepatocellular Carcinoma
AbstractThe study will evaluate the efficacy and safety of sunitinib (Arm A), given at 37.5 mg orally once daily, compared to sorafenib (Arm B), given orally at 400 mg twice daily, in patients with inoperable liver cancer. A total number of 1200 patients will be enrolled, 600 on Arm A and 600 on Arm B. Study treatment may be adjusted based on patient tolerance. and will be given until disease progression, occurrence of unacceptable toxicity, or other withdrawal criteria are met. After discontinuation of study treatment, patients will be followed up in order to collect information on further antineoplastic therapy and survival.
Tropical Journal of Pharmaceutical Research · 2020 · 0 citations · open access
Efficacy and safety of VEGFR inhibitors versus standard chemotherapy in Chinese patients with metastatic liver cancer: Results of a preliminary clinical trial
AbstractPurpose: To evaluate efficacy and safety of vandetanib with and without standard chemotherapy in Chinese patients with metastatic liver cancer.
 Methods: Patients with confirmed diagnosis of metastatic liver cancer were randomized to receive vandetanib (300 mg per day in 28 days cycle) intravenously or standard chemotherapy (FOLFOX4) plus best supportive care. Efficacy measures such as overall survival (OS), objective response rate (ORR), and progression-free survival (PFS) were assessed after study drug treatment. Safety of vandetanib and FOLFOX4 was also assessed. Survival time with respect to disease progression was also assessed.
 Results: Vandetanib + standard chemotherapy-based regimens showed significantly higher OS benefit when compared to vandetanib and chemotherapy alone. Objective response rate (ORR) was also favorable among the patients treated with combination therapy when compared with monotherapy. A similar trend was noted for PFS; treatment with vandetanib + chemotherapy showed significantly longer PFS when compared to vandetanib and chemotherapy alone, respectively. Trial results demonstrated that vandetanib as a monotherapy or in combination with standard chemotherapy appears to be safe.
 Conclusion: The results of this trial may aid clinicians to select appropriate therapeutic intervention for patients with metastatic liver cancer.
 Keywords: Vandetanib, Metastatic liver cancer, Chemotherapy, FOLFOX4, VEGFR inhibitors
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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