DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for hepatocellular carcinoma — screening already-approved drugs against its 47-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHepatocellular carcinoma maps to a 47-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 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
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
A 2012 study in mice with H22 hepatoma tested a modified adenovirus carrying the tumour suppressor gene PTEN, combined with the chemotherapy drug docetaxel. The virus was coated with mannan to improve delivery. Tumour inhibition rates were 48.69% for the unmodified virus alone, 49.98% for docetaxel alone, 75.88% for the mannan-modified virus alone, and 96.93% for the combination. Apoptosis was significantly higher with the combination than with any single agent. This is a single murine study; no human data exist for this approach.
Earlier reviews from 2006 and 2014 note that hepatocellular carcinoma is aggressive, heterogeneous, and requires multidisciplinary management including surgery, local ablation, and systemic therapy. A 2012 review of local and regional techniques describes radiofrequency ablation, alcohol injection, chemoembolisation, and yttrium-90 microspheres as methods to achieve tumour necrosis. These reviews do not report specific survival or response rates from controlled trials.
No abstract provides evidence from a randomised controlled trial in patients. The mouse study cannot be extrapolated to humans. The reviews call for better patient stratification and multimodality care but offer no new drug data. What is missing is any human trial of PTEN gene therapy for hepatocellular carcinoma, funding for such a trial, and a clear strategy for selecting patients who might benefit from gene therapy combined with chemotherapy.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Encyclopedia of Life Sciences · 2006 · 82 citations
Hepatocellular Carcinoma
AbstractAbstract The worldwide prevalence, unique geographical distribution and well‐established etiology of hepatocellular carcinoma have provided a strong impetus for elucidating mechanisms underlying the development of this aggressive malignancy. A better understanding of the specific molecular features of hepatocarcinogenesis has revealed clues for novel preventative and therapeutic strategies.
Sunitinib in Patients with Advanced Hepatocellular Carcinoma after Progression under Sorafenib Treatment
AbstractOBJECTIVE: To evaluate the safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma (HCC) after progression under sorafenib treatment. METHODS: Sunitinib was administered at 37.5 mg daily (4-weeks-on/2-weeks-off schedule) after progression under sorafenib treatment. Adverse events (AEs) were assessed using NCI-CTCAE v3.0, and tumor response was evaluated according to RECIST. Data were analyzed retrospectively. RESULTS: Eleven patients with metastatic disease were treated. Seven patients (64%) presented with no liver cirrhosis, including 3 patients with a history of liver transplantation. The first radiological follow-up showed stable disease in 40% of patients after marked radiological progression under sorafenib. The median time to progression was 3.2 months. Treatment was discontinued due to radiological progression (n = 9) or AEs (n = 2; hemorrhages) in all patients after 3.5 months. The median overall survival was 8.4 months. All patients with Child-Pugh class B liver cirrhosis suffered a clinical deterioration of liver function and died within 4 months due to tumor progression. CONCLUSIONS: Sunitinib provided modest antitumor activity in patients with advanced HCC after progression under sorafenib treatment. Patients with Child-Pugh class B liver cirrhosis might not receive a clinical benefit from this second-line approach. Hemorrhagic complications may represent a clinically relevant problem of sunitinib in patients with advanced HCC.
International Journal of Nanomedicine · 2012 · 15 citations · open access
Mannan-modified Ad5-PTEN treatment combined with docetaxel improves the therapeutic effect in H22 tumor-bearing mice
AbstractBACKGROUND: It has been reported that the tumor suppressor gene, PTEN, which is inactivated in many malignant tumors, plays an important role in apoptosis, cell cycle arrest, cell migration, and cell spread. For cancer gene therapy, one of the most important problems is low gene transfection efficiency. METHODS: In the present study, to take full advantage of adenovirus in gene expression, we prepared mannan-modified recombinant adenovirus using the PTEN gene (Man-Ad5-PTEN) and investigated the effect of Man-Ad5-PTEN combined with docetaxel (Man-Ad5-PTEN-docetaxel) on tumor growth in a murine model of hepatocellular carcinoma. RESULTS: Man-Ad5-PTEN effectively suppressed tumor growth and induced significant apoptosis of murine H22 hepatoma in vivo. Apoptosis levels in tumor-bearing mice treated with Man-Ad5-PTEN-docetaxel were significantly higher than those in tumor-bearing mice treated with naked Ad5-PTEN, Man-Ad5-PTEN, or docetaxel alone. Treatment with Man-Ad5-PTEN-docetaxel resulted in a significant inhibitory effect in this tumor model. Compared with the controls treated with phosphate-buffered solution, the tumor inhibition rate with naked Ad5-PTEN, docetaxel, Man-Ad5-PTEN, and Man-Ad5-PTEN-docetaxel was 48.69%, 49.98%, 75.88%, and 96.93%, respectively. CONCLUSION: These results suggest that combined treatment with Man-Ad5-PTEN and other chemotherapeutic agents may be a potent adjuvant therapeutic approach for the treatment of hepatocellular carcinoma.
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.
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