Combating primary and metastatic cancer by inhibiting cholesterol synthesis: Despite significant advances in breast and prostate cancer treatment, including the development of drugs that specifically target and eliminate certain kinds of tumor, many problems remain. Two overarching challenges are to develop safer, less toxic and more effective treatments than those currently available, and to advance therapies that more effectively prevent cancer metastasis (spread), which is a common cause of cancer death.
We must confront both challenges if we are to develop effective strategies that are capable of targeting particularly deadly types of cancer. Some breast and prostate cancers are particularly difficult to treat since they lack the targets that allow us to use less toxic drugs to destroy tumor cells. In the absence of such targets, the only drugs that can be used to treat these tumors are highly toxic, broad-spectrum compounds that not only result in a poor quality of life, but appear to function only as a stopgap measure. Despite such therapies, cancers frequently metastasize to vital organs such as lung, brain and bone, where tumors grow aggressively and often result in patient death. Consequently there is an urgent need for new, more effective, less toxic treatment strategies to combat breast and prostate cancers, especially those that lack specific targets for chemotherapy.
Recent studies in our laboratory showed that cholesterol-lowering drugs very effectively arrested the growth of both breast and prostate cancers, including those types that are resistant to currently used therapies. We found that cholesterol synthesis inhibitors not only blocked the growth of breast and prostate cancer cells, but also increased levels of a protein that is known to block cancer cell growth. Based on these initial observations, we propose to investigate in greater depth the potential of drugs already identified as cholesterol lowering agents, as agents that might be used chemotherapeutically to combat breast and prostate cancers that resist current treatments.
We will also conduct experiments to examine the effect of these compounds on tumor metastasis. Experiments will be performed in which cholesterol synthesis inhibitors will be given in conjunction with commonly used chemotherapeutic drugs to determine whether co-administration of the two agents elicits an additive effect that might effectively reduce the toxicity of currently used chemotherapeutics. We will also examine the effects of cholesterol synthesis inhibitors together with nontoxic, naturally occurring compounds found in fruits and plants, since there is evidence to suggest that certain plant-derived chemicals have anti-tumor properties. It is likely that such combinations will cause far fewer side effects than currently used chemotherapeutic drug regimens.
A successful outcome to our proposed studies would justify the immediate commencement of clinical trials aimed at testing the efficacy of cholesterol synthesis inhibitors, both alone and in combination with other drugs. The ultimate goal of such trials would be to make available more effective and safer therapies for patients suffering from primary and metastatic breast and prostate cancers, as well as other types of human cancers.