A new type of chemotherapy that was derived from a molecule in a Himalayan mushroom has been shown to be a powerful anti-cancer agent. It may one day offer a new option for patients suffering from cancer.
NUC-7738 was developed by Oxford researchers in collaboration with NuCana UK-based biopharmaceutical firm. Although it is still in experimental testing, the drug candidate is expected to be available soon as an anti-cancer medication. However, recent clinical trials results are encouraging.
Cordycepin is the active ingredient in NUC-7738. It was discovered in Ophiocordyceps Sinensis, a parasitic fungus that kills and mumifies moth larvae. It has been used for centuries as a traditional Chinese medicine herbal remedy.
Cordycepin (also known as 3’-deoxyadenosine or 3’-dA) is a naturally occurring nucleoside analog. It is reported to have a variety of anti-cancer and anti-oxidant effects. This is why the fungus has been called the most valuable parasite in the world.
However, naturally occurring cordycepin from O. sinensis has its limitations. It is quickly broken down in the bloodstream by the enzyme adenosine desminase (ADA) and then absorbed into the plasma for a half-life that lasts 1.6 minutes. It is also difficult to absorb into cells, which means that the molecule's effectiveness against cancer cells is severely diminished.
NUC-7738, which is designed to enhance cordycepin’s anti-cancer potential, makes use of several engineered advantages. It can enter cells without the need for nucleoside transporters like Human Equilibrative Nuclear Transporter 1.
NUC-7738 is not like naturally occurring cordycepin. It doesn't rely upon hENT1 for access to cells. Other tweaks to the molecule means it's preactivated (bypassing need to enzyme adenosine kinase) and resistant to being broken down in the bloodstream.
A new study on NUC-7738, which tested the drug candidate against a variety of human cancer cells, found that these modifications make it up to 40x more powerful than cordycepin.
Early results of NUC7738's first human clinical trial are positive. The Phase 1 trial involved 28 patients with advanced cancers that had not responded to conventional treatment. It began in 2019 and is currently ongoing.
Patients have shown encouraging signs of anti-tumor activity, as well as prolonged disease stabilization, and have tolerated weekly escalating doses (NUC-7738) of NUC-7738.
These findings support NUC-7738's clinical evaluation as a novel treatment for cancer.
It's a promising start but it will take some time before NUC7738 is available for patients outside of the trial.
The Phase 2 trial is in planning. Once safety has been confirmed and the recommended treatment regimen has been established for Phase 2, the plan will be put into motion.
These findings were published in Clinical Cancer Research.
