Hydroxychloroquine went from a relatively unknown malaria drug just a few years ago to a highly controversial treatment for COVID-19 during the pandemic. Now, doctors are uncovering surprising ways that this repurposed medication may be the answer for treating cancer.
Although cancer cells can become resistant to hydroxychloroquine, the new findings open the door for more effective combination treatments. Simply put, researchers have discovered how to team this versatile drug with other treatments which cover up any weaknesses hydroxychloroquine may have.
As scientists race to find new weapons in the war on cancer, some are taking a fresh look at old drugs that may have untapped cancer-fighting potential. One such drug is hydroxychloroquine, which has shown promise in attacking cancer cells by disrupting their ability to recycle resources.
Despite hydroxychloroquine’s effectiveness at cutting off this vital lifeline for cancer, clinical trials have been disappointing, with cancer cells often finding ways to overcome the drug’s effects. Now, researchers at the Medical University of South Carolina’s Hollings Cancer Center believe they’ve uncovered the key to this resistance – and it isn’t what they expected.
“We thought the main interaction of hydroxychloroquine with cancer was this process of autophagy, but it appears instead that processes unrelated to autophagy may be the most important for cancer cells to survive this therapy,” explains Joe Delaney, Ph.D., who led the study published in the journal Cell Cycle.
To be clear, autophagy is the cellular recycling process. This surprising finding opens up new possibilities for pairing hydroxychloroquine with other drugs that target these newly identified resistance mechanisms, potentially making the treatment more effective and longer-lasting.
A Two-Pronged Approach to Uncover Resistance
To understand how cancer cells were evading hydroxychloroquine, Delaney and his team took a comprehensive approach, using two different whole-genome screening methods to observe how cells adapted when continuously exposed to the drug.
“Targeting single proteins can be extremely effective to treat cancer,” Delaney notes. “However, the more specific the treatment becomes, the more likely resistance is to occur.”
“By using two completely different methods, we were able to home in on the true biological players in the system,” the researcher continues.
Rather than simply looking at which genes were turned on or off, the researchers were able to see the cascading changes happening across entire cellular pathways. This revealed that cancer cells weren’t modifying their recycling processes at all – instead, they were altering their cell division, metabolism, and export mechanisms to survive the hydroxychloroquine onslaught.
Paving the Way for Combination Treatments
These findings set the stage for developing new combination treatments that could boost the power of hydroxychloroquine. By pairing it with drugs targeting the cell division, metabolism, or export pathways that cancer cells rely on, researchers hope to prevent resistance from developing.
“Our study has identified the potential mechanisms that we will need to target with a second drug to prevent resistance against hydroxychloroquine,” says Delaney.
Source: https://studyfinds.org/hydroxychloroquine-cancer-treatment/
