Chloroquine-chemotherapy combination holds potential for metastatic breast cancer treatment

An anti-malaria drug used for more than 60 years is now being studied for use in breast cancer patients whose disease has not responded to traditional chemotherapy treatment.

Dr. Jenny Chang, director of the Methodist Cancer Center in Houston, is leading an investigator-initiated study to look at the efficacy and safety of chloroquine, used in combination with chemotherapy, as a possible treatment for patients with advanced or metastatic breast cancer.

The combination of chloroquine and standard chemotherapy already has proven effective in mice models with this disease.

"Our team of clinicians and researchers from both the Methodist Cancer Center and The Methodist Hospital Research Institute applied mathematical and bioinformatics models to screen for existing FDA-approved medications that might be effective against cancer stem cells," said Chang. "We identified chloroquine as potential cancer stem cell killer."

The primary goal of this clinical study is to better understand how cancer therapy works on different patients. Chang's team is focusing on the response of chloroquine used in combination with Taxane (Paclitaxel) or Taxane-like drugs (Abraxane, Ixabepilone or Docetaxel). The active ingredient in Taxane-like drugs is Paclitaxel, a natural product with antitumor activity.

Cancer cells go through a process called autophagy, which means "self-eating," a process of killing some of the body's cells that are old or under stress. Cells typically maintain a constant pH level at all times. When chloroquine was introduced into mice models with metastatic breast cancer, pH levels increased in certain components of the cells enough to kill the cancer stem cells.

Approximately 6,000 unique FDA-approved drugs exist today for health issues such as hypertension, diabetes and infectious diseases. With limiting funds flowing into new drug development, Chang said it is important to look at existing—and more affordable—drugs to treat a variety of diseases.

"We're very hopeful that this is a new paradigm that we can apply, repurposing old drugs for 5 cents a day that may make an impact in reversing treatment-resistance in women with breast cancer," said Chang, a breast medical oncologist.

Physicians began using chloroquine in the late 1940s for the prevention and treatment of malaria, after United States government-sponsored clinical trials showed that the drug had a significant impact as an anti-malarial drug. Chloroquine mildly suppresses the immune system, and it is used in some autoimmune disorders, such as rheumatoid arthritis and lupus. Chloroquine is also being studied as a treatment in patients with relapsed multiple myeloma, pancreatic cancer, glioblastoma multiforme, and small cell lung cancer.

Previous research stemming from a chloroquine vaccination program in Tanzania showed the incidence of Burkitts lymphoma fell by 75 percent. Two years after the study ended the incidence of Burkitt's lymphoma returned to baseline. Chang said these research results are an indication that chloroquine may also be used for prevention as well as treatment.

Source:

 Methodist Cancer Center

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