Often, people think cancer research is about developing new treatments. But finding ways to prevent cancer is also important. More than 200,000 Canadians are expected to be diagnosed with cancer this year, and this number will keep increasing as our population grows and ages, placing a significant burden on the health care system.
We know that about half of all cancer cases can be prevented through healthy living and policies that protect the health of Canadians. Cancer prevention research has often focused on changing behaviours and shaping the environment in which we live. The Canadian Cancer Society continues to support this kind of prevention research.
Yet, many cancers may not be preventable by lifestyle and environmental changes alone. Researchers are also exploring other ways to prevent cancer, including:
- Immunoprevention – using the immune system
- Chemoprevention – taking a drug or supplement
- Genetic research – identifying genetic changes that increase a person’s risk of cancer
The immune system monitors the body and attacks bacteria, viruses and other “foreign” material. It can also be trained or stimulated to look for cancer-causing infections or pre-cancerous cells, eliminating them before they become problematic. This is called immunoprevention.
Vaccines to prevent cancer-causing infections
A virus vaccine typically includes a weakened or inactive form of the virus or a piece of a virus containing an immune system signal called an antigen. The immune system recognizes the antigen as a threat and produces antibodies that stimulate an immune system attack. The antibodies are stored in the immune system’s “memory,” and if the immune system is exposed to the antigen on a live virus, it can mount a response quickly and eliminate the virus before it causes harm.
Certain viruses cause infections that can lead to cancer, but vaccines are able to prevent these infections.
HPV vaccine prevents cervical cancer
Human papillomavirus (HPV) infection is very common, with about 75% of sexually active men and women having at least one HPV infection in their lifetime. Most HPV infections go away on their own, but others can persist and cause cancer. HPV causes at least 6 types of cancer, including cervical cancer.
Over the past decade, all provinces and territories across Canada have implemented school-based HPV vaccination programs for girls. In that short time, we’ve already seen fewer women developing abnormal cervical tissue changes – the first step in cancer – providing support that the vaccination programs will be effective in preventing cervical cancer.
“The HPV vaccine is one of the biggest cancer prevention success stories. It is simple and cost effective to deliver, and it will have a global impact in preventing cervical cancer,” says Dr Miriam Rosin, Director of the BC Oral Cancer Prevention Program.
Mouth and throat cancers could also be prevented
HPV is also linked to other cancers, including others forms of genital cancers and certain mouth and throat cancers. HPV-related mouth and throat cancers affect more men than women, and there is currently no screening option for these cancers. When diagnosed late, treatments are less effective and more invasive and disfiguring, leaving side effects long after treatment.
Thanks in part to advocacy efforts by the Canadian Cancer Society and others, all provinces have extended their school-based HPV vaccination programs to include boys, which should help to prevent mouth and throat cancers caused by HPV.
“To me, this is a question of health equity. Boys and girls can both benefit from the vaccine,” says Dr Rosin. “We’re still learning about the biology of HPV-related mouth and throat cancer, but we already have an opportunity to prevent it, and that’s very exciting.”
Researchers are working on developing vaccines for other cancer-causing infections as well, but with the exception of the hepatitis B vaccine, there is still a long way to go before any are available to the public.
Only a few types of cancer are caused by viruses, so virus vaccines – while effective – aren’t the only immunoprevention solutions. Another strategy is to target precancer or cancer cells directly using a tumour vaccine.
In the lab, researchers can create a vaccine that is designed to look for an antigen, or marker, specific to the surface of tumour cells. Similar to a virus vaccine, after the tumour vaccine is injected, the immune system recognizes the antigen as a threat and produces antibodies against it. Following vaccination, the immune system is ready to attack when it finds a cell with a tumour antigen. This strategy is being tested as a form of cancer treatment, but it could be useful for prevention in people at high risk of developing a certain type of cancer.
Most research studying this strategy is still in early stages, but researchers have had some promising results in colon cancer.
Targeting colon cancer with an experimental vaccine
Researchers developed and tested a vaccine targeting an antigen called MUC1 that is often found on cells in a type of colon polyp that can develop into colon cancer. In a small clinical trial, they tested the vaccine in people who had recently had advanced precancerous colon polyps and were considered to be at high risk of developing colon cancer. The researchers found that the vaccine caused a strong immune response against the antigen. The trial was designed mainly to test safety, and the vaccine is now going through more testing to determine its effectiveness as a way to prevent colon cancer.
MUC1 is also found on pancreatic, breast, esophageal and lung cancer cells, so a vaccine against this antigen could potentially prevent a number of different cancers, though that possibility is still a long way off.
Training the immune system to eliminate cells with cancer-like markers could be an effective way to prevent some forms of cancer that have “precancerous” cells. But cancer can be very sneaky. A cell that is becoming cancerous changes frequently, and an antigen that the immune system recognizes may no longer be “visible” to stimulate an immune attack. In some cases, a more general immune system response is needed.
Immune system modulators
Immune system modulators do not target specific antigens, but instead stimulate a broader immune system response.
This approach does not have the specificity of vaccines, but that is actually part of its strategy. Cancer can be hard to treat because of the variety of tumour antigens. It may be difficult, if not impossible, to develop vaccines against every antigen, and these antigens might also change as tumours evolve. The benefit of stimulating the immune system generally is that you can still have an anticancer effect, even if the tumour’s cells change.
Checkpoint inhibitors are a promising group of immune system modulator drugs that are approved for lung cancer and melanoma treatment, though none are currently used for prevention. Given the promising results when used for treatment, researchers are looking for ways to stimulate immune system responses to prevent cancer, particularly in high-risk people.
Given the immune system’s critical role in protecting us from so many other diseases, its role in cancer prevention – through virus vaccines, tumour vaccines or immune system modulators – has enormous potential.
Cancer may also be prevented by taking a drug or supplement, a strategy called chemoprevention.
Drugs may be developed specifically for prevention, but often they are repurposed from drugs used in cancer treatment or from drugs used for entirely different diseases.
Because healthy people may take prevention drugs for years, potential drugs face some significant hurdles to be approved. They should be affordable and safe, with little to no side effects.
In some cancers, such as some forms of breast cancer, hormones promote cancer growth. In these cases, hormone therapy might help prevent the disease.
Hormone therapy blocks the activity of a hormone or prevents the hormone from being made, stopping cancer growth. This can be effective for treatment, but researchers are also testing whether using the same therapy earlier could stop cancer from developing.
Hormone therapy for breast cancer prevention
Estrogen receptor positive (ER+) breast cancers need the hormone estrogen to grow. Some hormone therapy drugs called selective estrogen receptor modulators (SERMs), which include tamoxifen (Nolvadex, Tamofen) and raloxifene (Evista), prevent estrogen from promoting breast cell growth.
These drugs have been successful in treating ER+ breast cancer, and clinical trials also showed that they could prevent invasive breast cancer in high-risk women. Concerns about the side effects of these drugs, which can include hot flashes, an increased risk of heart disease or stroke and an increased risk of uterine cancer, have limited their use in the prevention setting.
Aromatase inhibitors, which include exemestane (Aromasin) and anastrozole (Arimidex), work slightly differently. They prevent the body from making estrogen in the adrenal gland, shutting down the growth pathways in breast cells that need estrogen.
Clinical trials, including a CCS-funded trial testing exemestane, have provided evidence that aromatase inhibitors can prevent breast cancer with generally mild side effects. Researchers haven’t done as much research on this class of drugs yet, and the drugs currently aren’t approved for breast cancer prevention. But they have exciting potential and research is ongoing.
Repurposed generic drugs
Repurposing drugs used for other chronic conditions is a particularly promising strategy for chemoprevention. Drugs like this are known to be safe, can be taken for a long time and are often inexpensive. Aspirin and metformin are the focus of a lot of chemoprevention research.
Aspirin may have cancer prevention potential
Acetylsalicylic acid (Aspirin) can help relieve pain, fever and inflammation, and can be taken to help prevent heart disease. It may also have potential for cancer prevention.
Multiple clinical trials suggest that Aspirin is effective at preventing colorectal cancer, and perhaps other cancers as well, but questions remain:
- How might Aspirin prevent cancer? It may be related to treating and preventing inflammation involving an immune system response, both of which are often involved in cancer development.
- Are there specific groups of people who benefit more from Aspirin than others? Identifying who would benefit the most from Aspirin would allow for a targeted approach to prevention.
- What is the best dose? The dose needs to be high enough to be effective but low enough for safe daily use.
While the research so far is promising and continuing, at this point there is not enough information to recommend using Aspirin for cancer prevention.
Metformin may be repurposed for cancer prevention
Metformin (Glucophage) is a diabetes drug that helps lower blood sugar. There is some evidence from lab-based research that it may also slow or prevent cell growth, reducing the risk of cancer, but it is not yet clear whether metformin is an effective cancer prevention drug.
Clinical trials studying metformin as a prevention drug in people at high risk for certain cancers, including breast and colon cancer, are ongoing and in time will hopefully provide more evidence about whether metformin is useful in this context. For now, the jury is still out, and currently metformin is not recommended or approved for cancer prevention.
As with Aspirin, researchers need to know more about how metformin might work to prevent cancer. With that information, they will know how to better measure metformin’s effects and design clinical trials that should give clearer results.
Cancer develops when genetic mutations in a cell cause changes to activities that control cell growth. As a result, genetic research is essential for understanding how cancer can be prevented.
“Genetic research can uncover the biology behind cancer at a molecular level, giving us a better understanding of how cancer starts in the first place,” says Dr Mohammad Akbari, director of the Research Molecular Genetics Laboratory at Women’s College Hospital and assistant professor at the Dalla Lana School of Public Health at the University of Toronto. “It can help us identify people at high risk of cancer, but also understand how environmental and lifestyle factors change our genes and may lead to cancer.”
It can also help researchers develop effective strategies to prevent cancer.
Identifying genes associated with cancer
Many gene mutations increase the risk of certain cancers. For example, mutations in the BRCA1 and BRCA2 genes substantially increase the risk of breast and ovarian cancers, and possibly also prostate and pancreatic cancers. Gene mutations are also involved in Lynch Syndrome, which increases the risk of colon and uterine cancers, among others.
Thanks to powerful new technologies for analyzing genetic information, researchers can identify large numbers of gene mutations and other variations in the DNA that are associated with a higher risk of cancer. Researchers may then be able to screen people to look for these features.
Complexity of genetic information is a significant challenge
Despite the promise of this type of research, the sheer volume of information produced makes it difficult to know what is clinically useful.
“The human genome is incredibly complex, and there’s so much that we still need to learn about it,” says Dr Akbari. “There are many changes that happen in genomes as cells become cancerous, and the genome constantly evolves during the lifetime of a tumour cell, making the situation even more complicated.”
Another challenge is that even if we know a person has a mutation that increases their cancer risk, there often isn’t a lot that can be done to prevent the cancer. For example, women with BRCA mutations or people with Lynch syndrome are offered more screening and may opt for surgery to remove the tissue at high risk. Ideally, though, high-risk people would have better, less invasive options to prevent cancer, not just catch it early.
At this time, we don’t have tailored, non-invasive prevention drugs to counteract specific mutations. To develop them, we need to understand more about how the mutated and normal genes work.
Understanding what genes do
By understanding precisely how mutations or variations in certain genes increase cancer risk, researchers can then develop or use existing drugs that precisely target those mechanisms to prevent cancer from developing. This is a relatively new field of research, but this strategy will be tested in a breast cancer clinical trial.
In women with a BRCA1 mutation, researchers have identified a molecule called RANK-L that is involved in breast cancer cell growth. Preventing the activity of RANK-L could be an effective way to prevent cells from growing out of control and becoming cancer. Researchers are planning a clinical trial to test whether an osteoporosis drug that blocks RANK-L is effective in preventing breast cancer in women with a BRCA1 mutation.
Genetic research needs to be combined with other strategies
Genetic information alone is unlikely to prevent cancer. But once researchers know the genetic mutations that lead to cancer, they may be able to develop and apply immunoprevention or chemoprevention strategies that specifically block or correct the activity of the gene mutation. They can also identify the people who would benefit the most from these prevention strategies, allowing for more targeted approaches.
“We need to do more to prevent cancer in the first place, and genetic research is an important part of this strategy,” says Dr Akbari.
Researchers are studying many different ways to prevent cancer, including immunoprevention, chemoprevention and genetic research. Each field is making significant progress, but there is still a lot of work to be done before any can be used outside of the lab and clinical trials.
Clinical trials testing prevention strategies are particularly difficult, often needing more participants and longer time frames than treatment trials to be able to show definitive effectiveness. Because these drugs are given to healthy people, the side effects must also be minimal.
To address some of these challenges, many researchers are aiming to identify high-risk people through genetic research and test specific prevention strategies tailored to those groups. This may have a greater chance of success than trying to find one strategy that works for everyone.
With the burden of cancer set to increase in the coming years, we need to prevent cancer in many different ways, including leading healthy lifestyles and implementing health-protecting policies. At the same time, research is poised to lead to targeted strategies for people at high risk and help to reduce the number of people diagnosed with cancer in the future.
Eileen Hoftyzer, BSc and Carolyn Goard, PhD