Friday January 20 2012
Many people take statins to control their cholesterol
A daily dose of statins has “been shown to block the growth and spread of tumours,” according to the Daily Express. The newspaper reported that common cholesterol-lowering drugs “could be the key to beating cancer”.
The news is based on laboratory research into the role of a specific genetic mutation in the development of breast cancer. The research was mainly carried out in cell cultures, and did not test drugs on humans.
During their experiment researchers grew cells generated from breast cancer tumours carrying the mutation, which is often found in cancers. The researchers then interfered with the effects of this gene mutation, leading approximately half the cells to revert to a more normal structure.
Exploring this phenomenon further they then identified how this gene affects the cells, and tested drugs to interfere with this mechanism. Treating the breast cancer cells with simvastatin, a commonly used statin drug, reduced cancer cell growth and increased cancer cell death to an even greater extent than interfering with the gene mutation alone.
This study provides a potential new target for the treatment of breast cancer, and perhaps other cancers. However, significantly more research will be required before we know if statins or related new treatments can be used as treatments for breast or other cancers.
Where did the story come from?
The study was carried out by researchers from Columbia University in the US and other institutes throughout the US, Japan and Norway. It was funded by the US National Institutes of Health and The Breast Cancer Research Foundation. The study was published in the peer-reviewed scientific journal Cell.
This research was generally covered appropriately in the media. Both the Daily Express and The Daily Telegraph reported on the early stage of this research, and pointed to the fact that clinical trials would need to be conducted to confirm the study’s results. In news coverage, there was some suggestion that statin use among patients with high cholesterol has been proven to lower cancer risk, but this is not the case.
What kind of research was this?
This was a laboratory study that sought to investigate the role of a specific gene mutation in the development of breast cancer. Such studies are a necessary early step to identify possible targets for drug therapies.
As part of this research, scientists also looked at how these chemicals could interfere with the effects of this mutated gene. One of these chemicals was a statin, a type of drug prescribed to patients to lower their cholesterol.
Although this drug is already used in humans, this was early research into their effects on cancer cells. If this early research proves promising, further animal and human research will be necessary to determine whether statins could be an effective treatment for breast cancer patients.
Developing a new treatment is a long process and can take several years. Drugs that are already being used for another use in humans may reach human trials more quickly than completely untested drugs. However, it is still likely to take some time before statins could be approved as a cancer treatment.
What did the research involve?
This research centred on a gene called p53 that contains the code for producing a protein that suppresses the formation of tumours. When this gene becomes mutated, it produces an abnormal form of the protein.
In this study, the researchers first generated cell cultures (cells that can be grown indefinitely in the laboratory) from breast cancer tumours containing a mutation of the p53 gene. They then genetically manipulated these cells to block the action of this mutated gene, preventing it from successfully producing the abnormal p53 protein. They then looked at what effect this had on the structure of the cells when grown in a 3D culture in the laboratory, as cancer cells have different characteristic shapes and behaviour compared to normal cells. They also looked at the effect of introducing a mutated form of the p53 gene into non-cancerous breast cells.
Through further experiments looking at the genes being switched on and off in cells carrying the p53 mutation, the researchers identified the specific biochemical sequence of events or ‘pathway’ through which the genetic mutation was leading to cells becoming cancerous. This pathway is involved in creating cholesterol and can be blocked by statins, drugs that are already widely used to reduce patients’ cholesterol.
The researchers next treated the breast cancer cells with several different statins and assessed the effect on the cells structure and behaviour. They compared how cell structure was affected by using drugs to directly interrupt the pathway with the gene, as they had in their first set of experiments. The researchers also looked at the effect of a particular statin, simvastatin, on the growth of these tumour cells if they were implanted into mice.
Finally, they looked at whether the pathways identified in their cell culture studies also seemed to be disrupted in breast cancer tissue collected from 812 women. They also assessed whether changes to this pathway were related to the women’s survival.
What were the basic results?
The researchers found that interfering with the mutated p53 gene in tumour cells caused them to revert to a more normal appearance. Secondly, when a mutant version of the p53 gene was introduced into non-cancerous breast cells, they took on the appearance of cancerous cells.
The researchers found that the pathway involved in generating cholesterol was playing a role in the effects of p53 in their cells in the laboratory. Breast cancer tissue from women also showed that the same pathway is affected in women who carry the p53 mutation. Women in whom this pathway was most active had the shortest survival.
When the researchers took tumour cells carrying the p53 mutation and treated them with simvastatin, a commonly used cholesterol-lowering drug, they found a reduction in tumour cell growth, an increase in tumour cells death, and a reduction in the invasiveness of the tumour cells into the surrounding tissue. They found that these changes in structure were more dramatic than those seen when they directly interfered with the mutated gene using genetic engineering. Simvastatin also reduced the growth of the cancer cells if they were implanted into mice.
How did the researchers interpret the results?
The researchers say that their results indicate that a mutation of the p53 gene is ‘necessary and sufficient’ to generate cancer cell growth in the laboratory. They say that statins were effective at interfering with this tumour generation, and had effects on cell growth, death and invasiveness into surrounding tissue.
This was an early stage laboratory study that demonstrated that a specific mutation in a gene called p53 has a role in the generation of cancerous cells. It identified a potentially valuable target for drug treatments in the form of statins.
The researchers say that normal p53 genes act to suppress tumours, but when mutated, they can lead to the growth and progression of many cancers. They add that their study has identified the pathway through which this works. This pathway has been shown to be involved in cancerous cells’ growth, survival, spread and invasiveness into surrounding tissue.
An existing drug, a cholesterol-lowering statin, was found to interfere with the effects of this mutation in both cells in the laboratory and in mice. The fact that this drug is already used in humans may mean that if it continues to show promise in further cell and animal research, it can be tested in humans more quickly than a completely new drug. However, the early stage of this research means that it will likely be years before we know if they are an effective treatment for cancer.
This study provides exciting, if early, evidence of a potential role for a widely available drug in the treatment of cancer. More information is needed, however, to answer several important questions:
- Do statins have this effect only on breast cancer cells or will other cancer cells respond as well?
- Will statins reduce the growth and spread of cancer cells in humans?
- Are statins sufficient on their own as a potential treatment, or will other treatments be required as well? If others are required, how do statins interact with other treatments?
- Is there any existing evidence of lower cancer rates among statin users?
This study could be an important first step in the development of a new treatment for breast, and perhaps other, cancers. However, many questions remain unanswered, and it is not possible to say as yet whether statins or related drugs will ultimately be useful as cancer treatments.