DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for adult hepatocellular 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 moduleAdult hepatocellular 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
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Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Structures already discussed alongside adult hepatocellular carcinoma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Structure of the monomeric (V948R)gefitinib/erlotinib resistant double mutant (L858R+T790M) EGFR kinase domain co-crystallized — Gefitinib has a real, experimentally solved structure in complex with this target (PDB 4I22, 1.71 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 iredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4I22 · 1.71 Å · ligand Gefitinib (IRE). Experimental structure, not a prediction.
What the evidence adds up to
A 2017 phase I trial tested sorafenib combined with intermittent hepatic arterial infusion of cisplatin in fifteen patients with unresectable hepatocellular carcinoma. Dose-limiting toxicities appeared at sorafenib 800 mg and cisplatin 20 mg/m²; the recommended dose was sorafenib 400 mg and cisplatin 30 mg/m². The disease control rate was 73.3%. The authors concluded the regimen is feasible but called for further evaluation in a randomised controlled trial.
A 2018 study reported the synthesis of SP94-modified polypyrrole-BSA-ICG nanoparticles intended as a theranostic agent combining photoacoustic and near-infrared fluorescence imaging with photothermal therapy. In preclinical experiments these nanoparticles showed stability in physiological solution, higher tumour accumulation than unmodified nanoparticles, and minimal uptake by liver and spleen. The authors state that a single laser irradiation event killed the tumour with no recurrence, but this was in an animal model, not in human patients.
A 2012 review described local and regional techniques for hepatocellular carcinoma, including radiofrequency ablation, alcohol or acetic acid injection, embolisation with or without chemotherapeutic drugs, and injection of yttrium-90 labelled microspheres. The review asserted that these techniques have improved disease-free and overall survival, but provided no specific numerical data from trials.
A 2014 commentary argued that current treatment guidelines do not fully reflect patient heterogeneity and that a multidisciplinary approach involving hepatologists, surgeons, interventional radiologists, and radiation oncologists is needed to improve survival. No new trial data were presented.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The Oncologist · 2007 · 53 citations · open access
Hepatocellular Carcinoma: The Role of the North American GI Steering Committee Hepatobiliary Task Force and the Advent of Effective Drug Therapy
AbstractHepatocellular carcinoma (HCC) is a disease that requires multidisciplinary management. There has been no widely accepted standard for systemic therapy for this disease until recently. This article briefly discusses the management of earlier stage HCC, then focuses on newer agents with promise, particularly sorafenib, a drug that appears to be the new standard of care for advanced disease.
Targeted polypyrrole nanoparticles for the identification and treatment of hepatocellular carcinoma
AbstractEarly identification and treatment of hepatocellular carcinoma is very important for improving the prognosis and survival rate of the patient. To enhance the visualization and treatment efficiency of HCC, a theranostic agent has been developed that combines photoacoustic/fluorescence imaging with photothermal therapy for cancer. We report the synthesis of multifunctional theranostic SP94-modified polypyrrole (PPy)-BSA-ICG nanoparticles by a simple method. The multifunctional theranostic agent helped to combine two modes of imaging modalities, i.e. photoacoustic and near infrared (NIR) fluorescence imaging, together with photothermal therapy. These nanoparticles exhibited an excellent stability in physiological solutions (PBS, pH 7.4 at 37 °C), a higher tumor accumulation as compared to the unmodified nanoparticles, and minimal nonspecific uptake by other normal organs such as liver and spleen. Most importantly, the nanoparticles could effectively kill the tumor through photothermal therapy with no tumor recurrence upon a single laser irradiation event. These results indicate that SP94-modified PPy-BSA-ICG is potentially a promising theranostic agent for image-guided cancer therapy as it overcomes the limitations of each of the imaging modalities and thus improves the therapeutic efficiency and reduces the side effects.
World Journal of Gastroenterology · 2005 · 26 citations · open access
Antitumor effect of Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, combined with cytotoxic agent on murine hepatocellular carcinoma
AbstractAIM: To investigate the inhibitory effect of gefitinib combined with cytotoxic agent cisplatin (CDDP) on hepatocellular carcinoma (HCC). METHODS: Female Kunming mice and H22 hepatocarcinoma cells were used. Gefitinib at daily dose of 100 mg/kg body weight (BW) or lecithin liquid was given by gastrogavage once a day for 5 or 10 successive days. CDDP or normal saline (NS) was administered intraperitoneally (i.p.) once a day for 5 successive days. Mice were randomly divided into control group (lecithin, or NS, i.p.), CDDP group (daily dose, 1.2 mg/kg BW; d1-5, or d6-10), Gefitinib (d1-5, or d6-10, or d1-10), and Gefitinib combined with CDDP groups. The inhibitory rate (IR) of tumor, net BW, spleen index (SI), thymus index (TI) and the amount of peripheral blood cells of mice were detected on the 12th experiment day. RESULTS: The growth of HCC in mice was inhibited by Gefitinib alone (IR: 41% in d1-10 group and 30% in d1-5 group, respectively) or CDDP alone (IR: 32-54% in d1-5 group or d6-10 group). The highest inhibitory effect (IR: 56%) on HCC growth was observed in Gefitinib (d1-10) combined with CDDP (d1-5) group. Higher inhibition was also observed in CDDP (d1-5) followed by Gefitinib (d6-10) group than that in Gefitinib (d1-5) followed by CDDP (d6-10) group (IR: 61% vs 36%, P < 0.01) in the independent study. Net BW, SI, TI and the amount of blood cells of mice in Gefitinib alone group were not significantly different from those in control groups. CONCLUSION: Gefitinib can significantly inhibit the growth of murine H22 hepatocellular carcinoma. If Gefitinib is used after CDDP treatment in animal experiments, the inhibitory effect could be enhanced.
Efficacy and safety of the oxaliplatin-based chemotherapy in the treatment of advanced primary hepatocellular carcinoma
AbstractBACKGROUND: Many clinical studies have demonstrated the survival benefits of oxaliplatin-based chemotherapy for advanced hepatocellular carcinoma patients. Therefore, we aim to evaluate the efficacy and safety of oxaliplatin-based chemotherapy in patients with advanced hepatocellular carcinoma by conducting a meta-analysis of prospective studies. METHODS: A comprehensive literature search was performed using the PubMed, Cochrane Library, EMBASE, and Web of Science databases from their inception to June 2016. Only prospective studies evaluating oxaliplatin-based chemotherapy in patients with advanced hepatocellular carcinoma were selected. The main outcomes included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and main adverse events. RESULTS: Ten prospective studies involving 525 patients were included. The pooled ORR, 1-year PFS, and OS were 14.4% (95% confidence interval [CI] 9.2-19.6%), 9.3% (95%CI 10-28%), and 35.7% (95%CI 27-44%), respectively, for oxaliplatin-based chemotherapy. The median PFS and OS were 4.7 and 9.4 months, respectively. The incidences of grade 3/4 toxicities of neutropenia, thrombopenia, anemia, neurotoxicity, diarrhea, and nausea/vomiting were 17.2%, 9.2%, 6.0%, 4.8%, 3.1%, and 1.8%, respectively. Subgroup analysis revealed that the pooled ORR was 13.9% (95%CI 6.8-21%) in Asian patients and 12.8% (95%CI 6.8-18.7%) in Western patients. For Asian patients, the median PFS and OS were 4.2 and 9.2 months, and the 1-year PFS and OS were 12.5% and 30.5%, respectively. For Western patients, the median PFS and OS were 4.7 and 9.5 months, and the 1-year PFS and OS were 19.6% and 42.4%, respectively. There were no significant differences in the ORR, 1-year PFS, and OS (P > 0.05) between Asian and Western patients. CONCLUSIONS: Oxaliplatin-based chemotherapy appears to be effective and safe for the treatment of advanced hepatocellular carcinoma.
Comparative analysis of efficacy and safety between D-TACE + HAIC + lenvatinib and D-TACE + lenvatinib in the treatment of unresectable massive hepatocellular carcinoma
AbstractOBJECTIVE: The aim of this study was to investigate the efficacy and safety of the combined treatment regimen of D-TACE, HAIC, and Lenvatinib in patients with massive hepatocellular carcinoma, with the goal of providing a safer and more effective therapeutic strategy for individuals suffering from massive hepatocellular carcinoma. MATERIALS AND METHODS: A retrospective analysis was conducted using clinical data from 118 patients with unresectable massive hepatocellular carcinoma who underwent treatment at the Interventional Department of Wuhan Union Hospital between June 2018 and December 2021. Based on the treatment approach, the patients were divided into two groups: the D-TACE + HAIC + Lenvatinib group (N = 54) and the D-TACE + Lenvatinib group (N = 64). The primary study endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) of the two groups. Additionally, the occurrence of treatment-related adverse events in both groups was considered as a secondary study endpoint. RESULTS: Following the treatment, the D-TACE + HAIC + Lenvatinib group exhibited significantly higher ORR and DCR compared to the D-TACE + Lenvatinib group (68.5% vs. 43.8%, 90.7% vs. 73.4%, P < 0.05). Moreover, the D-TACE + HAIC + Lenvatinib group demonstrated longer mPFS and mOS in comparison to the D-TACE + Lenvatinib group (8.6 months vs. 6.6 months, P = 0.005; 19.5 months vs. 14.1 months, P < 0.001). There was no statistically significant difference in the occurrence rate of common treatment-related adverse events between the TACE + HAIC + Lenvatinib group and the D-TACE + Lenvatinib group (P > 0.05). CONCLUSION: The combined treatment regimen of D-TACE, HAIC, and Lenvatinib demonstrated superior therapeutic efficacy and safety in managing unresectable massive hepatocellular carcinoma. This combination therapy may serve as a viable option for improving the prognosis of patients with unresectable massive hepatocellular carcinoma.
Phase I Study of Sorafenib in Combination with Intermittent Hepatic Arterial Infusion Chemotherapy for Unresectable Hepatocellular Carcinoma
AbstractObjectives: We conducted a phase I study of sorafenib and intermittent hepatic arterial infusion chemotherapy using cisplatin for unresectable hepatocellular carcinoma. Methods: Sorafenib was administered continuously, whereas cisplatin was administered once every 3 weeks. We estimated the safety and efficacy. Results: Fifteen patients were enrolled into this study. The dose-limiting toxicities occurred at sorafenib 800 mg and cisplatin 20 mg/m2. The recommended dose was at sorafenib 400 mg and cisplatin 30 mg/m2. The disease control rate was 73.3%. Conclusions: This treatment is feasible for unresectable hepatocellular carcinoma. Further evaluation of the regimen in a randomized controlled trial is warranted.
The Most Important Local and Regional Treatment Techniques of Hepatocellular Carcinoma and Their Effect over a Long Term Overall Survival
AbstractDuring the last years, many local and regional techniques have been introduced, helping, together with surgery, to treat the hepatocellular carcinoma, and contributing to an important improvement of disease free survival and overall survival of patients affected by this disease. These techniques, suitable also for metastatic lesions, can be performed as exclusive ones or following surgery, and help controlling tumor progression even when it is over any possible surgical approach. Local and regional therapies can be divided into two groups: in the first one we can consider the techniques using heat to obtain their effect, in the second one we consider those using chemotherapic drugs to obtain necrosis of the neoplastic tissue. Necrosis can be obtained through the energy produced by radiofrequency probes, through the alcohol or acetic acid injection or through the injection of embolyzing substances, also together with chemotherapic drugs, into the hepatic artery. Last but not least, the injection of yttrium labeled microspheres is available. These are injected into the hepatic artery and are able to cytoreduce the tumor through a local irradiation.
Journal of Liver Cancer · 2014 · 0 citations · open access
Directions for Future Hepatocellular Carcinoma Treatment Guidelines; Hepatologist’s Perspective: Systemic Approach to Multidisciplinary Treatment
AbstractHepatocellular carcinoma is one of the most important malignancies in Korea with high mortality rates. Although current guidelines define treatment algorithm by performance status, underlying liver function, size and number of hepatocellular carcinoma, those are not fully reflect the complexities of patients' characteristics and recently advanced available therapeutic options. Treatment can be optimized by available therapeutic options based on the patients' characteristics. Because of the heterogeneity in presentation among patients, it is now widely accepted that management of hepatocellular carcinoma requires multimodality and multidisciplinary treatment approaches involving hepatologists, surgeons, interventional radiologists, and radiation oncologists. These approaches are important in improving the survival of patients with hepatocellular carcinoma.
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.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
