Monthly Archives: July 2015

The Key to Unlocking Future Treatments for Brain Tumors

Ayah blog post picture

A molecule (key; yellow arrow) bound to the binding site of the appropriate fitting protein (lock).

In Canada, it is estimated that approximately 3000 people will be diagnosed with brain cancer this year1. Glioblastomas (also known as glioblastoma multiforme) are one of the most common and aggressive forms of brain tumors that form from star-shaped cells in the brain called astrocytes. These tumors can reproduce at very fast rates and invade other nearby cells2. As a result, glioblastomas are often ‘resistant’ to conventional treatments such as radio- and chemo-therapy, meaning that these tumors survive despite patients undergoing treatment. Unfortunately, this implies that survival rates remain relatively low. In fact, the 5 year overall survival rate for brain cancer is only 25%.1 Despite this medical prognosis, advances in cancer research are allowing scientists to gain a better understanding of the genetic and cell pathways causing brain cancer development, which may ultimately lead to new treatment strategies.

For example, in 2009, a study conducted at Columbia University found that two proteins – C/EBP and STAT3 – are active in approximately 60% of glioblastoma patients. When activated together, C/EBP and STAT3 “turn on” hundreds of genes that then go on to transform normal brain cells into aggressive cancer cells. Researchers discovered that when they “turned off” C/EBP and STAT3 in human glioblastoma cells, and then injected them into mice, tumor formation was completely blocked3.

The identification of C/EBP and STAT3 as 2 potentially major players in the formation of glioblastoma provided insight into the key mechanisms involved in transforming ordinary brain cells into glioblastoma cells. This finding presented a novel approach to therapy that had never before been implicated in brain cancer and led other researchers to question whether new drugs could be developed to block C/EBP and STAT3 activity as a form of treatment.

The laboratory of Dr Patrick Gunning, a researcher at the University of Toronto (Mississauga campus) took on this challenge. The research team tried to create drugs that specifically target STAT3. Their work focuses on creating new molecules that bind to STAT3 and prevent it from functioning, as a way to try and block the progression of brain tumours. However, designing these molecules is not an easy task. Proteins are very complex; each has a unique structure and function. It is useful to think of this design process as a key and lock analogy. The goal in drug design is to create a molecule or drug (the “key”) that will only bind to a particular part of a protein (“the lock”). As a result, researchers must ensure that the molecule (or key) they create specifically fits the lock (protein) and not other proteins found in the body.

The Gunning lab was able to develop a drug they referred to as compound 31 (or SH-4-54), which was able to significantly disturb the function of the STAT34. In other words, they found a promising key to fit into their specific “lock” of interest. When they injected compound 31 into mice that had glioblastoma tumor cells, the mice showed a decrease in STAT3 activity and a drop in the number of glioblastoma tumor cells. Their research concludes that this was likely due to the STAT3 protein’s reduced ability to “turn on” genes that may potentially contribute to tumor formation. Although further advancements need to be made to allow us to better understand the impact this potential new drug has on tumor cells, this research brings us one step closer in the development of new drugs for this disease. It also highlights the amount of research that is needed to go from “bench to bedside”. Science is continually discovering more about the biology of cancer, such as glioblastoma, and how these cancers develop. However, a significant amount of time and effort also goes into the development of drugs that are precise and are able to successfully target and stop the growth of cancer cells.

This article was written by Ayah Abdeldayem. She is a second year undergraduate student at the University of Toronto Mississauga pursuing a double major in Biology for Health Science and Chemistry. To learn more about Ayah and her passion for science check out our members page.

Further Readings and References

  1. http://www.cancer.ca/en/cancer-information/cancer-type/brain-spinal/statistics/?region=qc
  2. http://www.abta.org/brain-tumor-information/types-of-tumors/glioblastoma.html
  3. http://www.nature.com/nature/journal/v463/n7279/full/nature08712.html
  4. http://www.unboundmedicine.com/medline/citation/24900612/Potent_Targeting_of_the_STAT3_Protein_in_Brain_Cancer_Stem_Cells:_A_Promising_Route_for_Treating_Glioblastoma_ (please click on PMC free PDF)

RIOT Video Blog Episode 2: Who Are Cancer Researchers?

Curing cancer is a difficult prospect. Scientists all over the world are working hard to understand the disease and how to fight it. But who are these scientists and how exactly do they spend their days in the fight against cancer? In this video Dr. Catherine Brun will describe a typical cancer researcher and what the process of cancer research looks like from the ground level, through the eyes of a researcher. If you have ever wondered who actually does the research you hear about and how they do it, look no further than the video below!

Filming and editing done by Colin Seepersad. If you want to learn more about Catherine or Colin take a look at our members page.

Direct-to-consumer Genetic Testing: Considering the Benefits and Limitations of Genetic Testing in your Personal Health Care Routine

Genetic Testing Blog Picture

An example of results of DNA sequencing used in genetic testing (source).

If someone told you that you could learn about your chances to developing certain diseases, like cancer or Alzheimer’s – would you? As a result of advances in scientific technology, private companies are now offering genetic testing kits to consumers that provide insight into their own genetic make-up. People are often drawn to these tests as they claim to provide information related to risks of developing some forms of cancer, personal responses to medications, and other health information. Before purchasing such a test, it is important understand the facts and know what you can really gain from the results.

1) What is direct-to-consumer genetic testing?

Direct-to-consumer genetic testing is a type of genetic test marketed to consumers that provides access to individuals’ genetic information. Currently, these genetic tests are advertised to identify your response to medications, your ancestry, and of greatest interest, the risks of developing certain diseases such as Alzheimer’s, diabetes, and various types of cancer, such as breast. This type of test often does not involve a doctor or medical professional. This is in stark contrast to traditional genetic tests that are only available through healthcare providers, who order them for specific conditions, and interpret the results. With direct-to-consumer genetic tests, anyone can purchase a genetic test and have it mailed directly to their house. Consumers collect their own DNA sample at home, often by swabbing the inside of a cheek or spitting into a test tube, and then mailing it to a laboratory. Test results are delivered by mail or posted online. The price for at-home genetic testing ranges from a few hundred to thousands of dollars.

2) What are the benefits of direct-to-consumer genetic testing?

With direct-to-consumer genetic testing gaining popularity, one clear benefit is that people can be more proactive in their personal health care. Additionally, there is greater awareness of how genetics may factor into certain diseases, and the tests do offer the benefit of learning about ancestral origins.

3) What are the limitations of direct-to-consumer genetic tests?

Direct-to-consumer genetic testing has fairly significant limitations.  One critical issue is that without guidance from healthcare providers, consumers may not be able to effectively interpret information from these tests, leading to inaccurate, incomplete or misunderstood assumptions about their health. Even if the results were to be brought to a health care provider, they may not be able to analyze the data properly as most companies do not provide critical information, such as the accuracy of the results, for example, what research they used to determine whether your genetic sequence correlates to disease1. The vast majority of diseases tested for, such as cancer, involve a complex relationship between genes, lifestyle and environment that is yet to be fully understood. Therefore, receiving a result of an increased genetic risk for diseases like cancer is not a reliable indicator of whether you will or will not develop the disease. Ultimately, more research is needed to fully understand the benefits and limitations of direct-to-consumer genetic testing.

Additionally, consumers should be aware of how their genetic information will be stored and used after the testing is done. Although some consumers may want to contribute to science and choose to share health information that be can be used to make new discoveries, they should research how their genetic privacy will be protected to ensure their genetic information is not used in an unauthorized manner. In Canada, currently there are no laws preventing insurance companies from discriminating against people with increased genetic risk of disease. If a consumer’s genetic information is not kept private, it could potentially hurt their chance of obtaining life or health insurance2.

4) Should I use direct-to-consumer genetic testing in my healthcare routine?

In its current state, direct-to-consumer genetic testing has limited power to accurately predict future disease. It cannot adequately calculate an individual’s risk of developing complex diseases such as cancer as there is a complex relationship between genes, lifestyle and environment that lead to development of the disease. If you have a strong family history of certain cancers, such as breast cancer, it is best to talk to your health care provider. Genetic testing can be an exciting and novel tool to learn more about your ancestry and personal traits. However, genetics is only one of many factors contributing to an individual’s health. Environmental and lifestyle factors can also contribute to a person’s risk of developing many diseases, including cancer. As I mentioned above, these issues are best discussed with your healthcare provider, along with your family history, to gain a more complete picture of your health that cannot be addressed through direct-to-consumer genetic testing.

This article was written by Dr. Katherine Wright. Katherine finished her PhD at the University of Toronto in 2014, where she studied how breast cancer spreads from one part of the body to another, a process known as metastasis. To learn more about Katie and her research check out our members page.

References

  1. Limitations of Direct to Consumer Genetic Testing: http://ghr.nlm.nih.gov/handbook/testing/directtoconsumer
  1. Genetic Discrimination in Canada: http://www.ccgf-cceg.ca/en/about-genetic-discrimination