By: Joseph Longo
Faced with increasing costs for the development of new drugs, researchers are now looking to repurpose older drugs as a relatively quick and inexpensive way of improving treatment options for cancer patients. One promising class of drugs that is receiving increased attention is the statin family of cholesterol-lowering medication. Statins have been used for decades to manage high cholesterol, and chances are that either you or someone you know is taking statins for this purpose. More recently, many studies have reported a link between statin use and reduced cancer risk and/or cancer-related death [1-4]. These observations have generated much excitement, as statins are already used in the clinic, are relatively cheap and are fairly safe, and therefore can be immediately repurposed to improve cancer patient care.
Repurposing statins to exploit a cancer cell addiction
Statins block a key pathway in cells that is important for the production of cholesterol and other lipid molecules. By blocking this pathway, statins lower the amount of these products inside the cell. In cancer, the products of this specific pathway are in high demand, as cancer cells rely on them for growth and survival. It is still unknown exactly how statins kill cancer cells, but many studies have shown that statin effectively “starve” cancer cells of these crucial products that are necessary for them to thrive [5]. Ongoing research is focused on identifying the specific products within this pathway that cancer cells are addicted to that make them sensitive to statin treatment.
Transitioning statins to the cancer clinic
Rarely are cancer drugs prescribed as a single therapy; rather, a combination of therapies is often prescribed to increase the effectiveness of the treatment and reduce the risk of relapse. Similarly, if statins are going to be repurposed to treat cancer, they will likely be co-prescribed with other treatments. Hence, an important focus of many current studies is to identify new and effective statin-drug combinations. For example, a recent phase II clinical trial evaluated the combination of high-dose pravastatin (a type of statin) and standard chemotherapy for the treatment of relapsed acute myeloid leukemia (AML). The authors of the study reported a 75% response rate, with 74% of the responders experiencing complete remission when given the statin drug alongside chemotherapy [6].
Despite evidence like this that supports the use of statins in the cancer clinic, other clinical trials have reported that statins offer no additional benefit when combined with standard therapy [7]. We need to better understand why some patients respond to this therapy while others do not, and use this information to better identify the patients who will benefit from treatment with statins. Moreover, if we can better understand why some patients do not respond, then we can identify more effective drug combinations that will work in these patients. Along this line, a recent study screened 100 clinically approved compounds and identified that dipyridamole, a drug approved for stroke prevention, increased statin-induced cell death in AML and multiple myeloma cell lines [8]. The statin-dipyridamole combination was also effective at delaying tumour growth in an animal model and killing primary AML cells collected from patients. Future clinical trials will be needed to assess the safety and effectiveness of this drug combination in actual cancer patients.
To date, over 100 clinical trials have tested or are actively testing if statins, either alone or in combination with other therapies, are effective at treating cancer. As the results of these studies become available in the coming years, they will inform us how best to use these clinically approved drugs in the fight against cancer. If the results are positive, then we will be in a strong position to immediately improve cancer patient care.
This article was written by Joseph Longo. Joseph is currently pursuing a PhD in the Department of Medical Biophysics at the University of Toronto. He studies how statins can be used to treat cancer. To learn more about Joseph and his research, check out our members page.
References
[1] Poynter et al. (2005). Statins and the risk of colorectal cancer. New England Journal of Medicine 352:2184-2192.
[2] Platz et al. (2006). Statin drugs and risk of advanced prostate cancer. Journal of the National Cancer Institute 98:1819-1825.
[3] Ahern et al. (2011). Statin prescriptions and breast cancer recurrence risk: a Danish nation-wide prospective cohort study. Journal of the National Cancer Institute 103:1461-1468.
[4] Nielsen et al. (2012). Statin use and reduced cancer-related mortality. New England Journal of Medicine 367:1792-1802.
[5] Mullen et al. (2016). Interplay between cell signalling and the mevalonate pathway in cancer. Nature Reviews Cancer 16:718-731.
[6] Advani et al. (2014). SWOG0919: a phase II study of idarubicin and cytarabine in combination with pravastatin for relapsed acute myeloid leukaemia. British Journal of Haematology 167:233-237.
[7] Kim et al. (2014). Simvastatin plus capecitabine-cisplatin versus placebo plus capecitabine-cisplatin in patients with previously untreated advanced gastric cancer: a double-blind randomised phase 3 study. European Journal of Cancer 50:2822-2830.
[8] Pandyra et al. (2014). Immediate utility of two approved agents to target both the metabolic mevalonate pathway and its restorative feedback loop. Cancer Research 74:4772-4782.
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