Chemo and Malaria Drug Combo Takes the Fight to Cancer

Posted by Admin on March 22, 2012
The ability to block autophagy - the process of 'self-eating' within cells - is turning out to be a viable way to enhance the effectiveness of a wide variety of cancer treatments. More specifically, halting the action of an acidic inner cell part, which functions as the 'stomach' and processes proteins for recycling, is the main attack strategy.

Lead author, Ravi Amaravadi, M.D., and his associates have found that adding hydroxychloroquine (HCQ) – an FDA-approved drug used commonly for malaria and rheumatoid arthritis – to a number of existing cancer therapies, including chemotherapy, targeted therapy, radiation, and immunotherapy, can enhance the effectiveness of these drugs in laboratory models of treatment-resistant cancers.

The function of autophagy is amplified in cancer cells. In normal cells, it is a survival pathway that allows a cell to recycle damaged proteins when under duress and reuse the damaged parts to continue further growth.  However, cancer cells find themselves addicted to autophagy, since this function allows the cell to survive the nutrient limitations and oxygen deprivation commonly found within tumors. It’s also a likely explanation as to how some cancer cells are able to evade chemotherapies.

For the study, nearly 30 phase I and phase II clinical trials involving HCQ have been launched or are in planning stages in many different types of malignancies, including renal cell carcinoma, melanoma, colon cancer, multiple myeloma, prostate cancer, breast cancer, and others. The initial results of the study show promise.

According to Amaravadi, “Our assays performed on human blood and tissue samples indicate that high doses of HCQ are required to block autophagy in patients, and in some cases, such as in a brain tumor trial, these high doses, in combination with specific anticancer agents, can lead to toxicity for the tumor. As the first phase I trials of HCQ are being completed, it is clear that in most cases the high-dose HCQ, in combination with existing cancer therapy, is well tolerated."

Using HCQ combinations in randomized controlled trials to determine the efficacy of this approach are being planned.  While these  plans are being sorted, the team will conduct additional lab experiments to identify more specific inhibitors of autophagy and determine which patients are most likely to respond to this approach.

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