05/01/2025
AUSTRALIAN RAINFOREST TREE - SOURCE OF EFFECTIVE CANCER TREATMENT?!
The blushwood tree, Fontainea picrosperma, is a rainforest tree in Queensland, Australia that's the source of the anti-cancer drug EBC-46. News report from 2017. More details and links to research papers in comments below.
"Stanford University researchers (USA) have discovered a rapid and sustainable way to synthetically produce a promising compound right in the lab. The compound’s availability has been limited because its only currently known natural source is a single plant species that grows solely in a small rainforest region of Northeastern Australia.
The compound, designated EBC-46 and technically called Tigilanol Tiglate, works by promoting a localised immune response against tumours. The response breaks apart the tumour’s blood vessels and ultimately kills its cancerous cells.
EBC-46 recently entered into human clinical trials following its extremely high success rate in treating a kind of cancer in dogs.
Given its complex structure, however, EBC-46 had appeared synthetically inaccessible, meaning no plausible path seemed to exist for producing it practically in a laboratory. However, thanks to a clever process, the Stanford researchers demonstrated for the first time how to chemically transform an abundant, plant-based starting material into EBC-46.
As a bonus, this process can produce EBC-46 “analogs” – compounds that are chemically similar, but which could prove even more effective and potentially treat a surprisingly wide range of other serious maladies.
These diseases, which include AIDS, multiple sclerosis, and Alzheimer’s disease, all share biological pathways impacted by EBC-46’s target, a key enzyme called protein kinase C, or PKC.
In the research studies posted further below "An open label phase IIa study evaluating the preliminary efficacy of intratumoural tigilanol tiglate (TT) in advanced and/or metastatic soft tissue sarcoma (STS)" demonstrated extremely good results.
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Overview
Tigilanol tiglate (also known as EBC-46) is a naturally derived small molecule extracted from the fruit seeds of certain Fontainea species—commonly referred to as “blushwood trees,” which are native to the Atherton Tablelands in Far North Queensland, Australia. The compound first gained attention for its rapid tumor necrotic properties in preclinical models. Since then, a number of studies have investigated its effectiveness and safety for treating various cancers in both veterinary and human contexts.
Below is a summary of the key points regarding tigilanol tiglate, its mechanism of action, and the current state of research.
1. Source and Extraction
Blushwood trees (Fontainea picrosperma): The primary source of tigilanol tiglate is the seed of Fontainea picrosperma, though related species in the Fontainea genus may also contain similar compounds.
Isolation: The compound is isolated from the seed kernels and then purified under controlled conditions. Early studies led by QBiotics, an Australian biotech company, identified tigilanol tiglate (EBC-46) as the active anticancer ingredient.
2. Mechanism of Action
Activation of Protein Kinase C (PKC): Tigilanol tiglate is thought to activate PKC—a family of enzymes involved in several cellular processes, including cell growth, differentiation, and apoptosis. PKC activation can lead to the breakdown of the tumor vasculature.
Local Vascular Disruption: When injected directly into tumors, tigilanol tiglate causes rapid hemorrhagic necrosis of tumor cells. This is often followed by a robust wound-healing response that facilitates tumor sloughing and tissue regeneration.
Immune-Mediated Effects: Some studies suggest that beyond the direct vascular disruption and tumor cell death, tigilanol tiglate may induce local immune responses that help the body eliminate residual tumor cells.
3. Preclinical and Veterinary Research
Preclinical Studies:
Conducted in mouse models of melanoma, head and neck carcinoma, and other tumor types.
Demonstrated rapid tumor regression—sometimes within days of administration.
Encouraging efficacy with minimal systemic toxicity due to the localized delivery method (intratumoral injection).
Veterinary Applications:
Stelfonta® (tigilanol tiglate) is approved in certain regions (e.g., Europe, Australia, and the USA) for the treatment of non-metastatic cutaneous mast cell tumors in dogs.
Clinical studies in canines showed a high success rate in achieving complete tumor remission with a single intratumoral injection.
This veterinary success paved the way for further interest in human oncology trials.
4. Human Clinical Trials and Research
Early-Phase Trials
Phase I trials have focused on safety and determining the maximum tolerated dose.
Intratumoral injections in patients with accessible, solid tumors (e.g., melanoma, squamous cell carcinoma) have shown preliminary signs of efficacy and manageable side effects, primarily localized inflammation and swelling.
Phase II and Beyond
Ongoing clinical trials are expanding to evaluate efficacy in larger patient cohorts, different tumor types, and various administration protocols.
Researchers are investigating optimal dosing, scheduling, and combination strategies (e.g., with immunotherapies or chemotherapy).
Preliminary results suggest that tigilanol tiglate can induce localized tumor destruction and might promote beneficial immune responses, but further data are needed to confirm these findings in larger populations.
Safety Profile
Common adverse events relate to localized injection site reactions, such as swelling, redness, pain, and sometimes ulceration at the tumor site.
Systemic side effects have been less common, which aligns with its predominantly local mode of action.
5. Challenges and Future Directions
Route of Administration
Tigilanol tiglate currently shows the most promise when administered via direct intratumoral injection.
Investigators are exploring whether it can be adapted or formulated for other routes of administration, although the main mechanism relies heavily on local vascular disruption.
Tumor Accessibility
Because intratumoral injection is the primary method, tumor accessibility remains a limitation for deep-seated or hard-to-reach malignancies.
Combination Therapies
Researchers are examining the potential synergy between tigilanol tiglate and immunotherapies (e.g., checkpoint inhibitors), aiming to harness and enhance tumor-specific immune responses.
Combination with standard chemotherapy or targeted agents is also under investigation to determine if tigilanol tiglate can boost overall treatment efficacy.
Regulatory Progress
While it is approved for certain veterinary indications, human use is still under clinical investigation, and regulatory approval will depend on the outcomes of ongoing Phase II and future Phase III trials.
6. Selected References
De Ridder, T. R., et al. (2018). "Intratumoral injection of EBC-46 (tigilanol tiglate) results in tumor ablation and subsequent wound healing with little systemic activity." PLOS ONE, 13(5): e0198632.
Boyd, A. W., et al. (2014). "EBC-46, a novel PKC activator for locoregional treatment of cancer." Molecular Cancer Therapeutics, 13(11 Suppl). Abstract.
QBiotics Group – Company website and published updates on clinical trials for tigilanol tiglate. ( https://qbiotics.com/ )
Conclusion
Tigilanol tiglate (EBC-46) stands out as a promising anticancer agent derived from the blushwood tree, showing rapid tumor necrosis capabilities with a primarily local, rather than systemic, impact. Its success in veterinary oncology (particularly for canine mast cell tumors) has spurred further clinical investigations in humans. Current research is focused on refining intratumoral administration, understanding optimal dosing, and exploring combination regimens with other anticancer therapies. While many studies are still in early phases, the existing body of data provides a foundation for the continued clinical development of tigilanol tiglate as a novel, targeted approach to tumor treatment.
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