Diagnosing elusive cancers
Dr. Shairaz Baksh hopes his work on a tumour suppressor protein will lead to a test for hard to diagnose cancers.
Story by Tara Narwani/Illustration by Josh Holinaty
Early cancer detection can have a major impact on the success of cancer treatments. But early detection relies on the availability of effective methods for cancer screening, which are difficult to develop given the complexity of the disease.
Dr. Shairaz Baksh is hoping that the research done in his lab will lead to a novel diagnostic test for hard to diagnose cancers, such as pancreatic and lung cancer. His research focuses on an understanding of the tumour suppressor protein called RASSF1A that appears to play a central role in the development of many cancers. "RASSF1 was identified as a protein missing in a lot of cancer patients. The gene for RASSF1 is not actually deleted—it's just inactivated. In almost every cancer looked at, this gene is inactivated to some degree," explains Dr. Baksh. Furthermore, in non-cancerous cells near the cancerous ones, RASSF1 is also inactivated. These non-cancerous cells will eventually become malignant themselves. Results like this point to the potential of using RASSF1 as an early indicator of the disease.
Cancer cells are abnormal cells that grow uncontrollably. When functioning normally, RASSF1 acts as a tumour suppressor by triggering the death of these abnormal cells when they form, which inhibits their growth. Therefore, RASSF1 prevents or suppresses the formation of tumours.
According to Baksh, however, once a cell is cancerous, it wants to survive. "It'll do everything it can to trick the cell into thinking everything's okay," he says. As a result, genes such as RASSF1A that promote cell death are inactivated in cancer cells, whereas genes that encourage growth are amplified.
In addition to being silenced in a lot of cancers, Dr. Baksh and his colleagues also observed small changes in the genetic sequence of RASSF1, which are called polymorphisms, in particular types of cancer. He found that some of these polymorphisms were not only unable to suppress tumours but actively promoted tumour growth when tested in mice.
"This is telling us that, if RASSF1 is absent, tumours will form. But, if RASSF1 is mutated somehow, you can also have tumours that form," says Dr. Baksh.
Information such as this is vital for the development of an accurate diagnostic test for cancer. A test would not only have to determine the genetic presence or absence of RASSF1A, but also identify whether the gene contains any of these important polymorphisms.
Currently, Dr. Baksh is also investigating whether RASSF1A is involved in the link between chronic inflammation and cancer. It's known that one-third of cancers actually start with chronic inflammation, for example, inflammation in the gastrointestinal system leading to colorectal or colon cancer.
To test whether RASSF1A is inactivated during inflammation, Dr. Baksh has collected blood and tissue samples from over 350 inflammatory bowel disease patients (both Crohn's disease and ulcerative colitis patients) at the University of Alberta and Stollery Children's Hospital.
"We want to see if we can make the argument that this gene is inactivated in these patients, and that's why they're getting the inflammation causing their disease," explains Dr. Baksh.
These results could have significant implications for patient treatment. If inflammation can be reduced, patients could potentially be spared from also developing cancer in the future. Dr. Baksh's research, therefore, has implications for both inflammatory disease and cancer. His goal is to understand the abnormalities associated with both in order to improve diagnosis and patient care.
What keeps Dr. Baksh excited about his research is the fact that "my gene is not deleted but inactivated and that gives us hope to reinstate the function of a gene that could eliminate cancer cells and bring normality back to both cancer patients and patients with inflammatory disorders."