A War With Cancer & Infection

For cancer patients, exposure to molds and bacteria in the environment can have life-threatening consequences.

Aspergillus is a common mold found in the environment that can cause infection in immunocompromised patients.

Dear readers,  

Today marks day 14 of being with my father in the ICU. He is receiving excellent care at a tier one cancer center. These have been difficult times for him, me, and his whole family. He’s in critical, but stable condition on a ventilator fighting for his life against an aggressive cancer that has come back despite trying four different regimens of chemotherapy and immunotherapy over the past year. We have had good days and really bad ones. We are taking things day by day. Despite the tremendous challenges ahead, my father has shown awe-inspiring strength, perseverance, and fortitude in the face of this storm. Cancer is a cruel beast—a wily thief that strips the patient and their loved ones to the bones, to what we thought were our limits and well beyond. Please keep us in your thoughts and prayers for continued strength as we face the challenges that each day brings.

For Cancer Patients, Infection is Also a Threat

I’ve spent my career looking for solutions to the antibiotic resistance crisis, and while my dad fights this cancer, he is also fighting a lung infection. The immune system is an incredible thing when it is fully functional, but when it isn’t, there are plentiful microbes—bacteria, viruses, fungi—that can easily creep into the body and wreak havoc. One such dangerous microbe is the mold, Aspergillus, a pathogenic fungus responsible for aspergillosis, or a mold infection.

We encounter molds in the environment—both indoors and outdoors—every day. And for those of us with well-functioning immune systems, these mold encounters are generally harmless. But when our bodies are worn down, when our defenses are weakened, they can take up residence in the lungs, leading to the development of pneumonia.

Most antibiotics come from natural sources, but the most commonly used antifungal medications, the azoles, are synthetically made. This is largely due to the later focus on antifungal drug research. Interest in combating invasive fungal infections only gained traction in the 1980s. Before that, large-scale drug screenings were more focused on bacteria. So far, azoles are the only class of antifungals derived from synthetic compounds approved for systemic use.

Synthetic compounds, shaped by available technology and chemical creativity, tend to occupy a narrower range of chemical structures compared to natural products. While synthetic libraries are often used for targeted drug discovery, natural products are typically screened in whole-cell assays. Unfortunately, both methods face challenges in yielding clinically effective antifungals.

Voriconazole: A Synthetic Antifungal Drug

Voriconazole, a triazole like fluconazole, has become the standard treatment for invasive aspergillosis, including lung infections, due to its effectiveness over amphotericin B. Voriconazole works by targeting and inhibiting a key fungal enzyme, disrupting the production of ergosterol, an essential component of fungal cell membranes. It shows broad effectiveness against many common fungi, including Candida species and Aspergillus species.

Structural features of antifungal drugs fluconazole and voriconazole. Image source.

There are four classes of antifungal drugs: polyenes (like various forms of amphotericin B), triazoles (such as fluconazole, itraconazole, and voriconazole), allylamines (such as terbinafine and naftifine) and echinocandins (like caspofungin). Treatment strategies involve either intravenous therapy or transitioning from intravenous to oral treatment, with only azoles suitable for the latter.

Physicians often struggle to identify mold infections early—it may take days to weeks to get a proper identification on a mold found in lung wash samples. This delay sometimes leads to the prophylactic use of voriconazole without sufficient clinical data. Voriconazole marks significant progress in treating invasive aspergillosis, demonstrating better efficacy and patient survival rates compared to another antifungal drug, amphotericin B. Studies also show voriconazole is better tolerated by patients, making it a first-line option.

Early detection and timely treatment are crucial in managing these infections. Voriconazole’s true value may become clearer as diagnostic and treatment strategies improve, ensuring patients who need the therapy receive it while avoiding unnecessary exposure for others.

The Takeaway

Patients with a compromised immune system, such as people living with HIV or cancer patients receiving chemotherapy, are at greater risk of infection by microbes in the environment that normally wouldn’t affect them when in good health. If there is anything I’ve learned over the past two weeks bedside with my dad in the ICU, it is that treatment of an immune-compromised patient in critical condition is a complex process requiring many specialists managing the function of different organ systems. The more IV lines, ports, and catheters required to deliver treatment, the more the risk for infection rises. The importance of filling the pipeline for new antimicrobial drugs with new classes of antifungals and antibacterials has never been greater. The story of voriconazole highlights the possibility of synthetic drug development and this doesn’t dampen the critical importance of the natural products discovery. When we combine these dual strengths, great things can happen.

Yours in health, Dr. Q

---

Cassandra L. Quave, Ph.D. is a Guggenheim Fellow, CNN Champion for Change, Fellow of the National Academy of Inventors, recipient of The National Academies Award for Excellence in Science Communication, and award-winning author of The Plant Hunter. Her day job is as professor and herbarium curator at Emory University School of Medicine, where she leads a group of research scientists studying medicinal plants to find new life-saving drugs from nature. She hosts the Foodie Pharmacology podcast and writes the Nature’s Pharmacy newsletter to share the science behind natural medicines. To support her effort, consider a paid or founding subscription or donation to her lab research.

---