A Phase I clinical trial of a chemical identified in a parasitic Himalayan fungus was found to kill tumor cells, boosting hopes that it could pave the way for more effective cancer treatments.
NUC-7738, which was developed by researchers at the University of Oxford in collaboration with the UK-based biopharmaceutical company NuCana, is still in the early stages of development and is not yet available as an anti-cancer medication - but newly reported clinical trial results are promising for the drug candidate.
Cordycepin is the active ingredient in NUC-7738, and was first discovered in the parasitic fungus species Ophiocordyceps sinensis (commonly known as caterpillar fungus because it kills and mummifies moth larva) and has long been utilized as a herbal cure in traditional Chinese medicine.
Also known as 3'-deoxyadenosine (3'-dA), cordycepin is a nucleoside analog, which is a class of antiviral and antibacterial compounds that is viewed as a promising candidate for new cancer drugs.
The main issue with 3'-dA, however, is that it has a very low bioavailability, which means it does not easily find its way to cancer cells when consumed in its natural form. This is due to the fact that it is broken down within minutes after entering the bloodstream by an enzyme called adenosine deaminase (ADA).
Even if it remained intact, cordycepin cannot penetrate tumor cells on its own and requires the assistance of a nucleoside transporter known as hENT1. Once within a cell, it must be processed by an enzyme called adenosine kinase (ADK) before it can exert its anti-cancer properties.
NUC-7738 uses a number of tailored advantages to boost cordycepin's anticancer potential, including the ability to penetrate cells without the help of nucleoside transporters like hENT1.
Unlike naturally occurring cordycepin, NUC-7738 does not rely on hENT1 to gain access to cells, and other changes to the molecule mean it's pre-activated (without the requirement for the enzyme adenosine kinase) and resistant to breaking down in the circulation, with built-in ADA protection.
When tested against a variety of human cancer cell lines, these modifications make the drug candidate's anti-cancer effects up to 40 times more powerful than cordycepin.
Furthermore, preliminary results from NUC-7738's first in-human clinical trial look to be favorable. The Phase 1 trial, which began in 2019 and is still ongoing, has so far included 28 patients with advanced tumors that have proven resistant to conventional treatment.
So far, weekly rising dosages of NUC-7738 administered to this cohort have been well tolerated, with "encouraging signals of anti-tumor activity and prolonged disease stabilization," according to the researchers' paper.
While this is an encouraging start, NUC-7738 will not be available to patients outside of the trial for some time.
The trial's Phase 2 is now in the planning stages.
The findings are reported in the journal Clinical Cancer Research.