Surprising link between cancer and fungal infections could be the key to new, more effective treatments

Two recent studies involving the Fungal Pathogenesis and Drug Discovery research group at The Westmead Institute for Medical Research (WIMR) have identified links between cancer and fungal infections that could ultimately lead to new, safer and more effective treatments.

How are cancer and fungal infections linked?

Fungal and human cells share many similar features, including their cellular organisation and how they regulate growth and respond to stress. This makes fungi a useful model for studying human diseases like cancer.

A promising new drug for brain cancer

A study recently published in the Journal of Medicinal Chemistry has led to the development of a new class of compounds that could help treat glioblastoma – one of the deadliest forms of brain cancer.

This study was a joint effort between the University of North Carolina, Vanderbilt University and WIMR.

WIMR researchers have been developing tools to find new antifungal drugs to treat deadly fungal infections in humans. One of these is a laboratory test that has been designed to measure the activity of a fungal enzyme called IPMK, which the team found plays a key role in fungal growth, energy use and virulence. This same enzyme also exists in humans and is thought to be important in cancer development.

Meanwhile, the US team had designed a set of potential drugs to target human IPMK but lacked a way to test how their compounds worked.

Head of WIMR’s Fungal Pathogenesis and Drug Discovery research group, Associate Professor Julie Djordjevic explains, “We were able to use our assay to help the US team test their new compounds. This collaborative effort led to the identification of a promising “first-generation” IPMK inhibitor with the potential to treat glioblastoma.

“This work highlights how cross-disciplinary research can lead to exciting breakthroughs with real potential to improve human health.”

Could a cancer drug be re-purposed to treat life-threatening fungal infections?

In a separate study published in mBio, the Fungal Pathogenesis and Drug Discovery research team discovered that a class of drugs known as CDK7 inhibitors, which are currently being developed as promising new treatments for cancer, can also kill fungi that cause life-threatening infections, including in cancer patients.

Fungal infections are a major global health issue causing more than 2.5 million deaths a year. These infections most often affect people with weakened immune systems such as those undergoing cancer treatment, people with HIV//AIDS or chronic lung disease, and organ transplant recipients.

Associate Professor Djordjevic says, “Fungal diseases are difficult to treat without causing side effects because fungi are biologically similar to human cells. Cancer patients already deal with many side effects from chemotherapy, so finding drugs that can fight both cancer and fungal infections could be a real game-changer.”

The research team focused on CDK7, a protein that helps both human and fungal cells grow and divide. In cancer cells, CDK7 activity is abnormally high, making these cells particularly dependent on it. Drugs that block CDK7 are now in clinical trials for several cancers.

As fungal cells share many similarities with human cells, the team hypothesised that cancer drugs targeting human CDK7 might also block fungal CDK7, offering a way to repurpose cancer drugs to treat fungal infections.

Their experiments confirmed this idea: several CDK7 inhibitors that show anti-cancer activity also stopped fungal growth. One compound, called SY-1365 (Mevociclib), was effective as an antifungal on its own.

Even more promising, low doses of SY-1365 and two related drugs – SY-5609 and Samuraciclib, which can be taken orally – worked well with existing antifungal medicines. This means that when the drugs were used together, smaller amounts of each were needed to kill the infection, reducing both toxicity and the risk of drug resistance.

Work done by WIMR’s Dr Pooja Sethiya also revealed that CDK7 plays essential roles in fungi, including gene regulation, RNA processing, and cell division, helping scientists better understand how these pathogens grow and survive.

The team found that CDK7 inhibitors were most effective against Cryptococcus neoformans and Cryptococcus gattii, two fungal species identified by the World Health Organization as priority pathogens. Ongoing studies are now testing these drugs to see whether they can protect against fungal infection in living organisms.

“CDK7 inhibitors have already been tested in cancer trials so we know a lot about their safety and dosage,” said Associate Professor Djordjevic. “That gives us a head start in exploring their potential as antifungal treatments.”

These findings identify CDK7 inhibitors as promising candidates for combination antifungal therapy, with the potential to make treatments safer and more effective and to give existing antifungal drugs a much-needed boost.

Funding: This work was supported by an NHMRC Ideas grant and seed grants from Sydney Infectious Disease (USYD), The Centre for Drug Discovery and Innovation (CDDI, USYD) and a REN grant (Westmead Hospital).