Repurposing Cancer Research to Defeat a Disfiguring Tropical Disease

While a widely recognized treatment exists for cutaneous leishmaniasis, a disfiguring tropical skin disease, it’s an arduous, toxic regimen that fails more than half the time.

Now, researchers from the University of Maryland and the Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM) in Colombia are launching a sophisticated new strategy that borrows a page from modern oncology.

Supported by a new $342,000 two-year research grant from the National Institute of Allergy and Infectious Diseases, the team is pivoting away from traditional drugs to focus on host-directed therapy. This approach seeks to treat the infection by repurposing tools originally designed to fight cancer—specifically, inhibitors that prevent diseased cells from “switching off” the body’s immune response. 

The funding supports Najib El-Sayed, a professor of cell biology and molecular genetics with an appointment in the University of Maryland Institute for Advanced Computer Studies; and Olga Fernández, coordinator of the Immunology and Cell Biology Laboratory at CIDEIM; to target a particularly devious subpopulation of the Leishmania parasite known as zymodeme 2.3.

“Understanding these pathways allows us to identify how the parasite triggers host cell mechanisms to enable its own survival,” said El-Sayed, who is also a member of UMD’s Center for Bioinformatics and Computational Biology and Institute for Health Computing.

In Colombia, patients infected with this 2.3 strain face a staggering 63% treatment failure rate—making them four times more likely to fail therapy than those with more sensitive strains. It is also capable of going dormant within the body only to reemerge years later.

The parasite’s survival hinges on a biological heist: It hijacks macrophages—the body’s primary immune defenders—and silences them by activating a metabolic “off-switch.” Malignant tumors exploit the exact same signaling pathway to evade detection. 

Using primary human cells from 55 healthy donors and 12 specific clinical strains of the parasite, the researchers are testing a trio of molecular “keys” to see if they can break this cloak. These include CB-668 and aryl hydrocarbon receptor inhibitors (AhRi)—to act as a molecular barrier to prevent the parasite from silencing the macrophages. 

In early tests using the inhibitor 1-MT, these tools successfully allowed immune cells to regain their primary weapon: a lethal burst of protective oxygen that destroys the invader.