Mushroom-derived chemotherapy shows promise

An employee processes Cordyceps flowers on the production line at a fungus company on August 7, 2020, in Suining, China. Liu Changsong/VCG via Getty Images
  • Researchers recently modified a metabolite derived from a Himalayan fungus. They believe it may help treat cancer.
  • Early results suggest that the modified fungal metabolite is well tolerated in people with advanced cancer and that it has anti-cancer effects.
  • The researchers are currently planning phase 2 clinical trials.

Over the last 71 years, hundreds of studies have found that cordycepin may haveTrusted Source beneficial effects on various health problems, including:

  • cancer
  • cardiac conditions
  • inflammation
  • mental health problems and issues with brain function
  • metabolic disorders
  • pain
  • respiratory conditions

Despite cordycepin’s success in cell cultures and animal studies, little research exists on the effects of cordycepin on people, because it breaks down quickly in the bloodstream. This means that only small amounts reach the target site.

Figuring out a way to make cordycepin more stable in the body could lead to new therapeutics for cancer and other conditions.

In a recent study, researchers led by the University of Oxford in the United Kingdom and biopharmaceutical company NuCana found a way to make cordycepin more stable in the body. They called their new drug NUC-7738 and conducted a phase 1 clinical trial in people with advanced cancer.

From cellular studies, the researchers learned that NUC-7738 was better able to reach cancer cells and generate high levels of anti-cancer metabolites than regular cordycepin.

Early results from clinical trials involving patients with treatment-resistant advanced stage tumors also showed that the novel chemotherapy drug was well tolerated and exhibited signs of anti-cancer activity.

“In this study, the authors show that a modified form of the cordycepin molecule, NUC-7738, makes it effective at lower concentrations and for longer,” Dr. Cornelia de Moor, Ph.D., told Medical News Today. Dr. de Moor is an associate professor in RNA biology at the University of Nottingham, U.K., and was not involved in the study.

“Excitingly, this appears to be not only true in cell culture and animals but also in cancer patients.”

ProTide technology

One of the main problems with using cordycepin to treat people is that it breaks down easily in the body upon contact with an enzyme known as adenosine deaminase (ADA). It also relies on a nucleoside transporter called hENT1 to reach cancer cells, and phosphorylating enzyme (ADK) to be converted into an anti-cancer metabolite.

To overcome these issues, the researchers modified cordycepin with ProTide technology, a novel approach to delivering drugs to cancer cells.

ProTide technology works by attaching small molecules to preactivated compounds to help them reach their target cells. Once reached, these small molecules break down, leaving the preactivated compounds to do their work.

Scientists already use this approach in Food and Drug Administration (FDA)-approved antiviral drugs, including remdesivir and sofosbuvir, for viral infections, including hepatitis CEbola, and COVID-19. The FDA also recently fast-tracked anti-cancer drug Acelarin, which uses the same technology.

Employing ProTide technology, the researchers synthesized several preactivated versions of cordycepin before selecting one — NUC-7738 — for further investigation.

They then tested NUC-7738 alongside regular cordycepin on a wide set of cancer cell lines. NUC-7738 was at least seven times more potent than regular cordycepin.

NUC-7738 performed particularly well on teratocarcinoma cells, which is a form of testicular cancer. These cells were over 40 times more sensitive to NUC-7738 than to cordycepin.

Next, the researchers conducted cellular tests to measure the effects of NUC-7738 on ADA, ADK, and hENT1. Unlike regular cordycepin, which was dependent on all three, NUC-7738 did not respond to inhibition of any of them.

The authors of the study then began an ongoing phase 1 clinical trial to test the drug in patients. As of June 1, 2021, they enrolled 28 people across the U.K. with various forms of advanced cancer, including melanomacolorectal cancer, and lung cancer, to receive doses of NUC-7738 ranging from 14 to 900 milligrams per meter squared.

Early results from this trial suggest that cancer patients tolerate well all doses of the drug. The researchers also noted signs of anti-tumor activity and prolonged disease stabilization, especially among those with immunotherapy-resistant melanoma.