The research — which reviewed more than 190 studies investigating how chloroquine (CQ) and hydroxychloroquine (HCQ) affect cancer cells — describes how the malaria drugs may increase tumor sensitivity to existing cancer treatments.
Based on their findings, first study author Ciska Verbaanderd, from the University of Leuven in Belgium, and her colleagues say that the drugs "deserve further clinical investigations in several cancer types."
The review was recently published in the journal ecancermedicalscience.
While the United States has seen a fall in cancer death rates in recent years, the disease remains a significant burden on public health. Last year, there were more than 1.6 million new cancer cases diagnosed in the U.S. and more than 595,000 cancer deaths.
Given that cancer is increasingly becoming resistant to existing therapies, there is a desperate need to uncover new ways to fight the disease.
Verbaanderd and colleagues believe that the drugs CQ and HCQ could help in this fight.
CQ and HCQ as cancer therapies
CQ and HCQ are medications used to prevent and treat malaria. They may also be used in the treatment of lupus and rheumatoid arthritis. A wealth of research, however, has suggested that these drugs may also have anti-cancer properties.
For their review, Verbaanderd and colleagues analyzed the results of more than 190 animal and human studies that assessed the effects of CQ and HCQ on different types of cancer.
According to the researchers, the aim of their review was "to inform further research and trials on repurposing CQ and HCQ as anti-cancer agents."
The team uncovered evidence to suggest that CQ and HCQ could be effective for the treatment of a number of cancers, including glioblastoma — which is a deadly brain cancer — lung cancer, and pancreatic cancer.
"CQ and HCQ have been studied in multiple preclinical cancer models," write the authors, "and have demonstrated activity on several cancer-supporting pathways and in combination with a broad range of other therapies."
"[...] The majority of these studies have reported an improved therapeutic efficacy as compared with monotherapy with existing anti-cancer drugs," they add.
The review also indicates that both drugs are "safe and tolerable" as an anti-cancer therapy, though current evidence suggests that HCQ might pose fewer side effects.
How can CQ and HCQ fight cancer?
According to the team, their review highlights a number of mechanisms by which CQ and HCQ could help to treat cancer.
Firstly, there is evidence to suggest that the drugs can inhibit autophagy, which is the process whereby cells devour their own damaged or unnecessary components.
"Autophagic properties such as nutrient recycling can support cancer cell survival," the authors note. "Moreover, key regulators of cell growth can be degraded and the DNA damage response can be suppressed through increased autophagy."
"Therefore, inhibition of autophagy can be an interesting anti-cancer strategy when cancer cells start depending on autophagy for survival."
The review also revealed that CQ and HCQ can block the CXCL12/CXCR4 signaling pathway, which previous research has associated with cancer progression.
Additionally, there is evidence that CQ can stabilize a protein called p53, which is a known tumor suppressor, and it may also help to normalize blood vessel dysfunction in tumors.
"The benefits of vessel normalization include a decrease in tumor hypoxia, reduced cancer cell intravasation and metastasis, and an increase in chemotherapeutic drug delivery and response," the authors explain.
Drugs could offer 'significant clinical benefit'
Overall, Verbaanderd and colleagues believe that their study has highlighted the potential benefits of CQ and HCQ as a cancer treatment, as well as the mechanisms behind their anti-cancer properties.
"The results from the review lead us to believe that these antimalarial drugs could offer significant clinical benefit for certain cancer patients, especially in combination with standard anti-cancer treatments. This should be confirmed by additional clinical results."
The team notes that there are 30 clinical trials currently investigating the effects of CQ and HCQ against various cancer types.
Based on their review, the researchers conclude that these trials should focus on the efficacy of these medications, as well as the best doses and methods of administration.