A molecule found in a parasitic Himalayan fungus has been found to kill tumor cells in a Phase I clinical trial, raising hopes that it may provide a foundation for more effective cancer treatments. Known as cordycepin, the compound is produced by the so-called caterpillar fungus, which is infamous for its penchant for killing and mummifying moth larvae.
The findings are reported in the journal Clinical Cancer Research.
Also known as 3'-deoxyadenosine (3'-dA), cordycepin belongs to a class of antiviral and antibacterial agents called nucleoside analogs, which are seen as highly promising candidates for new cancer drugs. Considered a potent antioxidant, 3'-dA has been a staple of traditional Chinese medicine for centuries.
However, the big problem with 3'-dA is that it has a very low bioavailability, which means it doesn’t easily find its way to cancer cells when ingested in its natural form. This is because it is broken down by an enzyme called adenosine deaminase (ADA) within minutes of entering the bloodstream.
Even if it remained intact, cordycepin can’t enter tumor cells on its own, and requires the assistance of a nucleoside transporter called hENT1. Once inside a cell, it must then be metabolized by an enzyme called adenosine kinase (ADK) before it can exert its anti-cancer effects.
To overcome these hurdles, a team of researchers modified cordycepin using ProTide technology. This involves adding a protective phosphoramidate cap to a molecule, thereby enabling it to resist being broken down before it reaches its target inside the body.
The study authors reveal that their modified compound, called NUC-7738, “overcomes the cancer resistance mechanisms that limit the activity of 3’-dA.”
“The ProTide NUC-7738 is resistant to ADA degradation and is capable of releasing active 3-dAMP into cells, where it is rapidly converted to the key anti-cancer metabolite,” they write. Importantly, this anti-tumor compound remained active for at least 50 hours and was shown to be between seven and 40 times more potent than natural cordycepin at destroying a range of different cancer cells.
Administering the drug to human cancer patients with advanced, treatment-resistant tumors, the researchers noted that the compound is “well tolerated and has demonstrated encouraging signals of anti-cancer activity.” Molecular analyses revealed that the drug appears to induce cancer cell death, primarily by disrupting key signaling pathways that enable the proliferation of these cells.
There’s still some way to go before NUC-7738 becomes available as a cancer treatment, although the researchers are already planning their Phase II clinical trial and believe that their drug could one day provide a life-saving option for cancer patients worldwide.