“You have cancer.” It’s one of the most feared sentences.
A cancer diagnosis can send a person – and their family – on a long and difficult journey.
At Lawson Health Research Institute, researchers are committed to improving every stage.
Discoveries are happening in the lab, in the clinic and in collaboration with other research areas. Some researchers focus on basic science while others are also physicians who treat patients.
Their goal is the same: advance our knowledge of the disease in order to develop new treatment and detection strategies.
The power of junk DNA
Dr. Fred Dick is improving this understanding with a new breakthrough in cancer genetics.
A Lawson scientist at London Health Sciences Centre (LHSC)’s London Regional Cancer Program, Dr. Dick specializes in the study of the Retinoblastoma protein (pRB). This protein is traditionally known to control the growth of individual cells and prevent the development of cancer.
Dr. Dick and his team discovered that pRB actually has another, more important role. It works with another protein, EZH2, to silence ‘junk DNA’.
“Most of the DNA in the human genome is junk DNA, also called repetitive sequences,” explains Dr. Dick. “They are leftover pieces of ancient infections that are no longer in existence.”
Junk DNA is believed to have no positive contribution to the human body. It’s kept silent and not expressed by our cells. If it is expressed, junk DNA can be reinserted into the human genome where it damages our genes and contributes to diseases like cancer.
The discovery shows that pRB helps EZH2 find its way to a cell’s junk DNA. EZH2 then adds a tag which tells the cell not to express the junk DNA.
Charles Ishak, PhD candidate, working in Dr. Fred Dick’s lab. Charles was first author on a study that showed the Retinoblastoma protein (pRB) helps to silence junk DNA.
The study predicts that EZH2 inhibitors, drugs that block EZH2, could be used to help the immune system target cancers. Blocking EZH2 in cancer cells will lead to the expression of junk DNA so that cancer cells appear to the immune system as if they are infected by a virus. The immune system could then target and kill those cells.
“With more knowledge of someone’s specific cancer, we can give the right mix of inhibitors and immunotherapy,” says Dr. Dick. “This will help target cancer right at the point where cells are expressing junk DNA.”
Enhanced prostate cancer imaging
Dr. Glenn Bauman is collaborating with Lawson Imaging scientists to improve the diagnosis and treatment of prostate cancer.
Dr. Bauman is a radiation oncologist at LHSC and a lead investigator on an Ontario Institutes of Cancer Research project titled SPIRIT, Smarter Prostate Imaging and Interventions. Dr. Bauman and his team were the first in Canada to capture highly specific prostate cancer images using a new molecule known as a prostate-specific membrane antigen (PSMA) probe. The PSMA probe is used in Positron Emissions Tomography (PET) scans to correctly diagnose cancer.
PET probes are injected into a patient where they then spread throughout the body and identify sites of disease. PET scans are often combined with Computed Tomography (CT) or Magnetic Resonance Imaging (MRI). This shows where the probe is concentrated, confirming precisely where the cancer is located.
There are common PET probes to image most cancers, but they have been less accurate in identifying prostate cancer.
The PSMA probe solves this problem by specifically targeting PSMA molecules, which are found on prostate cancer cells. The resulting images provide exceptional detail about a patient’s cancer, including the precise location and size of a tumour.
“The use of PSMA probes is a tremendous step forward in the management of prostate cancer,” says Dr. Bauman. “With more accurate detection, we can provide better and faster treatment.”
The next step is to work with researchers across Ontario to develop clinical trials to study the PSMA probe. Dr. Bauman believes it can also be used to measure responses to drug treatments and evaluate men whose cancer may have returned.
Lawson researchers were the first in Canada to use a PSMA probe to capture highly specific PET/MRI and PET/CT images from a prostate cancer patient. The MRI image (A) demonstrates a dark area in the posterior right side of the prostate (lower left part of the image) that is highly suspicious for prostate cancer. In the PET/MRI image (B), the bright yellow colour indicates where the PSMA probe was taken up in the prostate. This area corresponds to the suspicious area on the MRI scan (A).
Identifying the spread of disease
Lawson scientists are also revolutionizing the ability to track the spread of disease.
Dr. Alison Allan specializes in the study of metastasis. Metastasis, the spread of cancer from the original tumour to other sites in the body, is responsible for approximately 80 per cent of cancer deaths.
“Cancer cells can leave a tumour and enter the blood stream,” explains Dr. Allan. “Called circulating tumour cells (CTCs), these cells move throughout the body where they can invade other organs and tissues.”
Her lab has developed unique blood tests to track metastasis for different cancers by measuring the number of CTCs in a patient’s blood stream.
“The number of circulating cells predicts if a patient’s disease is progressing and if it might metastasize. A high number suggests that a patient’s cancer is spreading.”
Dr. Alison Allan specializes in the study of metastasis – the spread of cancer from the original tumour to other sites in the body.
With studies proving the effectiveness of these blood tests for a number of cancers, LHSC now offers the test to breast, prostate and colorectal cancer patients. LHSC is the only hospital in the country to offer the test.
It is used for patients who have just been diagnosed with metastatic cancer. Measuring the number of CTCs provides a real-time assessment of how a specific treatment is working.
The blood test can also be used for patients who are in remission, when their body no longer shows signs of the cancer. It helps monitor for remaining cancer and gives patients peace of mind.
Left: Circulating tumor cell (CTC) from a breast cancer patient undergoing chemotherapy. The CTC is stained to show cell death. Right: Breast cancer cell found circulating in the blood stream that was stained with a cancer stem cell marker.
Studies are currently underway for other types of cancer too.
One research team is looking at how the number of CTCs changes before and after standard treatments for esophageal cancer, such as chemotherapy and radiation.
“This is the first time the test has been used in the treatment of patients with early stage esophageal cancer,” says Dr. Richard Malthaner, director of Thoracic Surgery Research at LHSC.
“We anticipate using the results to predict which patients will be cured of their cancer and which patients might need additional treatment,” adds Dr. Edward Yu, radiation oncologist at LHSC. “The blood test could one day replace the multiple x-rays and CT scans that are currently used.”
Learn more about Dr. Allan’s work with CTCs:
Drs. Fred Dick, Glenn Bauman, Alison Allan, Richard Malthaner and Edward Yu are part of the Cancer research program at Lawson. Drs. Dick and Malthaner are Professors and Drs. Allan and Yu are Associate Professors at Western University’s Schulich School of Medicine & Dentistry. Dr. Bauman is a Professor and Chair of the Department of Oncology, Schulich School of Medicine & Dentistry at Western University and Chief of the Department of Oncology, London Health Sciences Centre.