You asked, our researchers answered!
On April 28th, we hosted a live webcast Latest Advances in Cancer Research. The researchers shared some of the latest discoveries in cancer research, as well as some of the new ways scientists are trying to treat this disease. We had a lot of questions asked during the webcast, here are the answers that the researchers have shared.
1. In an article in Scientific American last year on cancer, one writer actually used the word "resistance" in describing the actions of cancer cells. May you please give us more information on this?
I think the easiest way to explain the concept of resistance in biology comes from antibiotics. If you have ever had a bacterial infection and were prescribed antibiotics, you know that the doctor recommends you take the entire dose, even after you start to feel better before the full dose is finished. This is because there is some variability in how bacteria respond to the antibiotic, and some are more susceptible than others. If antibiotic treatment is stopped part-way through, before all of the bacteria are dead, only the most susceptible bacteria have been killed. The remaining bacteria in the group are more resilient to the antibiotic, and if given the opportunity to grow, can develop full-blown resistance, rendering the antibiotic ineffective.
Resistance of cancer cells works in the same way. Some cancer cells are more susceptible to treatment than others, and these will die early when treatment is applied. If the treatment kills all of the cancer cells, there is no chance that there will be any resistance because there are no cancer cells left. However, if there are some cancer cells left after treatment, they are likely cells that have a special resistance to the treatment. As these resilient cells divide, they produce more and more resilient cells. Some of these descendent cells might even develop greater resistance to the treatment. Over time, a cancer that is fully resistant to the original therapy becomes established. The way doctors get around this is to always give patients more than one drug or type of treatment because it is much harder for cancer cells to develop resistance to several treatments at once than it is to develop resistance against a single therapy.
2. Is chemotherapy a targeted therapy?
Chemotherapy is not considered a targeted therapy. The common definition of a targeted therapy is a treatment that only affects cancer cells, leaving normal cells alone. Chemotherapy is not directed specifically at cancer cells, but affects all rapidly dividing cells. This is why chemotherapy has side effects, like hair loss. Chemotherapy blocks pathways needed for rapid growth, or introduces a bit of DNA damage that a rapidly dividing cell doesn’t have time to repair. This approach has some specificity, in that cells that are not dividing or dividing slowly are not as affected. However, targeted therapy like Gleevec attempts to target only the cells that have a specific cancer-causing mutation.
3. Why can't we develop drugs that ONLY affect/kill/treat tumours rather than taking drugs that affect the whole body system?
Much research is dedicated to developing drugs that are specific to tumour cells, and do not affect normal cells. However, this can be a very challenging task. After all, tumour cells are our own cell “gone rogue” and it has been challenging to find treatments that differentiate between normal cells and tumour cells.
However, with our ever-increasing understanding of cancer and improvements in technology, scientists are constantly trying to produce highly targeted and more effective therapies. Examples of targeted therapy, or personalized medicine include Gleevec, Herceptin and Crizotinib, all of which are featured in the presentation. Some of the challenges associated with this approach are highlighted in our presentation.
Another strategy scientists are testing are oncolytic viruses, or cancer-fighting viruses, which are viruses that specifically target cancer cells, but leave normal cells relatively unharmed. This is an active area of research in Canada, including Ontario, and clinical trials are currently underway to determine whether this approach could be an effective way to treat cancer.
4. Why are there so many different types of chemotherapy drugs, if they kill all fast growing cells? Why can't we just use one kind of chemotherapy drug for every type of cancer?
Different chemotherapy drugs affect fast growing cells in different ways. Some drugs block molecules that tell a cell to grow, but there are several different pathways that can tell a cell to grow. It is important to use several drugs that affect different growth pathways to fight cancer. If only one chemotherapy drug was used to target one growth pathway, the cancer cell might just switch growth pathways and keep on growing.
5. On the webcast, you mentioned that Gleevec has few side effects; however, I know of someone who had major side effects from this drug. Can you please explain?
Side effects from drugs are to be expected and can be very different depending on the person. With any drug, it is best to consult with your doctor to review any potential side effects. Never hesitate to talk with your doctor about what you are experiencing when you are on medications. If you have any further questions about Gleevec or any of the other medications mentioned on the webcast, it is best to consult your health care provider.
6. These targeted drugs are quite expensive. How can a patient with no drug plan or limited plan take advantage of them?
The Canadian Cancer Society provides information about this topic. Please visit their website or call the Cancer Information Service (1-888-939-3333) to learn more.
7. Is Tamoxifen a targeted therapy?
Yes, Tamoxifen is a type of therapy that acts on the estrogen receptor found on the surface of some breast cancer cells. These cells have many estrogen receptors on their surface, and when activated by the hormone estrogen, they help cells divide and grow. Certain types of breast cancer are thought to be “addicted” to estrogen. Tamoxifen acts to block the action of the estrogen receptor, thereby depriving tumour cells of their proliferation signals, and causing them to die. It is considered to be a targeted therapy because it only affects cells that have these estrogen receptors. Other types of breast cancer do not express this receptor, and therefore wouldn’t benefit from Tamoxifen treatment.
8. Is Certinib a first line of therapy? Is it available in Canada?
According to the Health Canada website, it appears as though certinib has been approved for use for patients with ALK-positive, locally advanced or metastatic non-small cell lung cancer who have progressed on or were intolerant to crizotinib. With respect to any medication, it is best to consult your health care provider to learn more about cancer drugs, and what drug is right for you.
9. Where are T-cells located in the body? Can we increase the number of T-cells by medication, i.e., build a troop to battle the cancer cells?
T-cells are white blood cells and are part of your immune system. Like all blood cells, they are born in the bone marrow. T-cells become fully developed in the thymus, and this is why they are called T-cells (T for Thymus). It is possible to increase the number of T-cells to fight cancer. There is a therapy for melanoma, which involves taking a small number of cancer-fighting T-cells from your body, growing them in the lab, and re-introducing the large “troop” of T-cells back into the body to fight the cancer. This approach has had some success but it relies on amplifying an already existing population of T-cells that can target the cancer. If such cells cannot be isolated, this approach would not work.
10. Suppose cancer cells escape from the tumour. Can T-cells find those cells or does it have to be in a tumour to be attacked?
T-cells function by detecting the proteins on the surface of other cells. If they are able to access and identify tumour cells as being “foreign or abnormal”, they induce cell death. This is irrespective of whether the tumour cells are located at the site of the primary tumour, in a metastasis (site where the tumour has spread), or circulating in the blood. T-cells are currently being studied as a potential form of immunotherapy for cancer.
11. Does immunotherapy align with the theory that a healthy lifestyle - diet and physical activities - help fight cancer?
There is evidence that a healthy lifestyle, including eating healthy and exercise, boosts immune system function. We know that a healthy lifestyle is very important. Research has shown that almost half of all cancers could be prevented through healthy lifestyle choices and public policies. However, we are not aware of any current studies showing that the immune systems in people living these lifestyles are better at defending against cancer.
12. Do cancer stem cells behave the same way as the cancer cells in the developed tumour?
The theory behind cancer stem cells is that they are the only cancer cells capable of forming a full tumour. You can read more about cancer stem cells in one of our blog posts. This theory was developed based on observations that only certain pieces of a mouse tumour will cause tumour formation when transplanted into a healthy mouse. The pieces that did cause tumour formation contained what researchers called “cancer stem cells”. Cancer stem cells are also believed to grow more slowly than other tumour cells. Traditional chemotherapy targets cells that grow very quickly, as most cancer cells do. Thus, traditional therapies are not ideal for killing cancer stem cells. It is believed that recurrence of cancer after remission is due to persistence of cancer stem cells that have evaded treatment and have grown into a new cancer. Research is ongoing to figure out new ways to target and kill cancer stem cells.
13. There's myth that consuming too much sugar might lead to cancer. You mentioned cancer cells are hungry and feed on glucose. So, is the myth true?
There is no evidence that consuming too much sugar will directly lead to cancer. According to cancer.ca, all cells in your body consume sugar as they grow and divide, but eating sugar does not make cancer cells grow faster. Sugar is found naturally in foods, such as fruits and vegetables and is added to other foods like desserts and condiments to make them sweeter.
Every cell in your body requires sugar (glucose) for energy and your body needs this sugar to function normally. Research is ongoing to look at the effectiveness of limiting sugars in cancer patients to help in treatment, however more work needs to be done in this area of research.
14. What is the timeline for cancer treatments that are fast tracked?
The timeline for cancer treatments that are fast tracked varies depending upon the drug and what it is indicated for. A drug will typically be considered for fast tracking if there is no current treatment for a specific type of disease. For instance, Erivedge® (approved for patients with advanced metastatic basal cell carcinoma) was fast tracked to approval without a Phase III trial because of the lack of treatments for this population of patients. Nonetheless, every investigational drug (with the exception of drugs that are re-purposed) needs to go through Phase I and Phase II clinical trials to establish safety and efficacy before it can even be deemed applicable for fast tracking.
15. With so many "old "drugs to choose from, how are repurposing drugs chosen besides the ones mentioned in your presentation?
This is a tough question and the short answer is - it depends on data from the lab, findings in case-reports and legal issues.
As mentioned in the talk, most of the old drugs being repurposed for cancer treatment are serendipitous discoveries. Researchers now are actively mining through libraries of old drugs to determine whether they can be used to treat cancer. The old drugs that are being investigated are typically drugs that are off-patent or generic drugs because there is no legal issues associated with it. Potential anti-cancer properties are assessed in a lab by treating cultured cancer cells. If the old drug is successful in killing cancer cells, researchers can test this drug in animal models and then eventually clinical trials (Phase II and III) in a specific patient population. As for drugs that are patent-protected, it is at the discretion of the company to conduct additional research for other indications.
Alternatively, there could be indications from case-reports, which is a detailed report describing a patients’ symptoms, diagnosis, treatment and follow-up visits. For example, there could be multiple reports whereby a drug was given to a cancer patient to treat an unrelated disease and had a positive effect on their cancer. This drug may be considered for drug repurposing using methods described above (and in the presentation) can ensue.
16. Are these old drugs being repurposed under investigational status?
Yes, old drugs still need to undergo investigational status to determine its efficacy in the new disease (e.g. cancer treatment). In most (if not all) cases, Phase I studies are not necessary since the safety profile has already been determined previously. Instead old drugs are mainly tested for efficacy in Phase II or Phase III trials.
17. Is Thalidomide still available?
Thalidomide was banned worldwide in 1962 because of the severe birth defects it caused. However, in recent years, clinical trials have found that thalidomide is effective for treating a variety of conditions, including multiple myeloma. It was demonstrated that thalidomide could produce lasting complete or partial response, as well as disease stabilization in patients with multiple myeloma. As a result, in 2006 the US Food and Drug Administration granted approval of thalidomide in combination with dexamethasone for the treatment of multiple myeloma. It is now available in Canada through a controlled distribution program and is indicated for the treatment of patients with previously untreated multiple myeloma who are 65 years of age or older. It is best to consult your doctor if you have any further questions about thalidomide.
18. Which drug is similar to Thalidomide?
There are several drugs that are similar to thalidomide, including lenalidomide and promalidomide. Based on positive findings from several clinical studies, lenalidomide and promalidomide are approved by Health Canada for patients with multiple myeloma. They are considered “second-generation” drugs to thalidomide because they are substantially more potent and have better safety profiles than thalidomide. It should be highlighted that every patient is different and may respond to drugs differently (even if they are “similar” drugs). It is critical to have a consultation with a health care professional when discussing which drug is right for you.
19. What about the severe adverse effects of these old drugs? (Thalidomide)
Thalidomide was first approved in Europe in the late 1950s for the treatment of morning sickness in pregnant women. It was later discovered that the drug produced severe, life-threatening birth defects and was subsequently removed from the market. However, in recent years, clinical trials have found that thalidomide is effective for treating a variety of conditions, including multiple myeloma. Because thalidomide can cause birth defects, it is not used on women who are pregnant or at risk of becoming pregnant.
Results from clinical trials revealed additional serious side effects when receiving thalidomide for treatment of multiple myeloma. These include:
- Damage to peripheral nerves (resulting in numbness, tingling, pain and loss of sensation)
- Blood clots in veins and arteries
- In some cases, a higher risk of liver problems which may lead to death
Because of these potential harmful effects of thalidomide, it is only available under a controlled distribution program to ensure that the risk-benefit ratio is optimal for each patient prior to use. It is best to consult your doctor if you have any further questions about thalidomide and its side effects.
20. What about the polio vaccine? Is it being repurposed?
There is a lot of excitement around using a genetically engineered poliovirus to target brain cancer (Glioblastoma multiforme). This is not a classic example of repurposing, but rather a new discovery by using our existing knowledge of how cancer cells behave and leveraging the properties of polio virus biology. This type of research is known as oncolytic virus therapy. Scientists are testing whether oncolytic viruses, or cancer-fighting viruses, can specifically target cancer cells, but leave normal cells relatively unharmed. This is an active area of research in Canada, including Ontario, and clinical trials are currently underway to determine whether this approach could be an effective way to treat cancer.
21. I wonder, are there living things that are smaller than a virus or prions or viroids?
This is a bit of a grey area, in fact. Some scientists think that viruses, viroids and prions are not considered to be living things, because in order for something to be alive it must be able to reproduce independently. Viruses cannot do this by themselves; instead, they “hijack” the cell’s machinery in order to make more copies of themselves. Through numerous ways, viruses enter our cells, and use several of the cell’s enzymes to translate their genetic code into protein. Once many copies of the virus are made and assembled inside the cell, they rupture the cell and are free to go on and attack other cells. This is the stage at which we feel the symptoms of viral infections, such as when you develop the common cold. Similarly to viruses, viroids invade plant cells and replicate in the same manner.
On the other hand, prions are not made up of genetic material, so the distinction between living and not-living is more striking. Prions are proteins that do not assemble appropriately, and therefore cannot fulfil their normal roles. Interestingly, prions have the ability to induce normally folded proteins to adopt the prion’s misfolded pattern, and also lose their normal function. The mechanism by which prions induce normal protein misfolding is not well understood, and is an active area of research.
To answer your question, the smallest known organism is called Mycoplasma gallicepticum. It is an extremely small bacterium that lives in the urinary and respiratory tracts of primates, and is 200 to 300 nanometers in size. To give you a sense of scale, E. coli is about 500 nanometers, and the head of a single human sperm cell is 5000 nanometers! M gallicepticum is the smallest living organism known to date. As science progresses, who knows what else we will discover!
We would like to thank our researchers, Mat, Natalia, and Sue once again for the great webcast. If you missed it, you can watch it on demand now.