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Personalizing Cancer Medicine Through Proteins
In the fight against cancer, personalized medicine has become a powerful tool—and the Jewish General Hospital is leading the way for this innovative approach to treatment through proteomics.
What is proteomics?
Simply put, protein analysis. But through this analysis, researchers can determine if a patient’s proteins have undergone gene mutation, which can help them find disease patterns and potentially more successful modes of individualized treatment.
“Genomics shows us a list of the ingredients of the body — while proteomics shows us what those ingredients produce. Understanding what’s going on in your body at the protein level may lead to a new understanding of how cancer happens.” – Danny Hillis*
“If genomics is a photograph, proteomics is a movie.” – Bruce Wright – Head, Division of Medical Sciences, University of Victoria
Proteomics and the Jewish General Hospital
With the creation of not only a Clinical Proteomics Laboratory at the Segal Cancer Centre but also the first pan-Canadian proteomics program, the JGH is continually advancing the impact that proteomics and personalized medicine can have for cancer patients locally and around the world.
The development of new diagnostic tools and targeted therapies means potentially better outcomes for those with tumour metastasis, urological cancer and many other forms of disease.
*William Daniel “Danny” Hillis is an American inventor, engineer, mathematician, entrepreneur, and author. He is Judge Widney Professor of Engineering and Medicine at the University of Southern California
Personalizing Cancer Medicine Through Proteins
Dr. Christoph Borchers: Adapting Proteomics in The Era of Precision Medicine
Dr. Christoph Borchers is the Director of the Segal Cancer Proteomics Centre.
His research focuses on the improvement, development and application of proteomics technologies with a major focus on techniques for quantitative targeted proteomics for clinical diagnostics.
In recent years, it has become increasingly clear that each cancer is individual and that generalized treatment for patients is no longer appropriate.
In the era of precision medicine, cancer patients are increasingly selected for specific treatment with novel drugs based on genomic profiling for genetic mutations. While, in theory, this is a powerful approach for ensuring that each patient receives optimal treatment, response rates are still often unexpectedly low. Depending on the type of cancer, up to 50% of patients may not respond to a drug selected based on their genomic status.
One reason is that the genome defines only the potential template of an organism (genotype) and is static, while biological processes are highly dynamic and depend on a variety of factors: environmental, dietary, age, health status, etc.
Thus, genomics will fail to distinguish the caterpillar from the butterfly, as they are two distinct life cycles (phenotypes) of the same organism and therefore share the identical genome. They can be clearly distinguished, however, based on their protein fingerprint (the proteome). Accordingly, an individual’s cancer cannot be completely understood relying on a genomics approach.
Combining proteomics and genomics to improve precision medicine & the prediction of an individualized treatment plan for cancer patients.
In order to improve precision medicine and to enable the prediction of an individualized treatment plan for a cancer patient, it is crucial to obtain precise information about the proteome. Several critical questions can only be addressed by combining proteomics and genomics, now called “proteogenomics”.
- Which genes and mutations are actually active and are being translated into proteins in a tumor? A tumor cell contains more than 10,000 different proteins and not every predicted mutation is present or relevant.
- How many molecules of each protein are really present in the tumor? This copy number can range from a few to a several million molecules per cell and is often changed in tumors compared to healthy cells or tissues.
- Is the activity of these proteins and their communication altered? Dysregulated cellular communication (signaling pathways) is one of the main causes for cancer.
Proteogenomic analysis of tumor biopsies allows the researcher to fully understand the molecular basis of individual tumors by combining precise information of its genotype and phenotype so that clinicians can specifically select (and develop) treatment strategies that not only effectively kill all of the cancer cells but also prevent relapse in the long term.
FURTHERING RESEARCH AT THE SEGAL CANCER PROTEOMICS CENTRE:
At the Segal Cancer Proteomics Centre, we have a clear proteogenomics strategy. Our analytical methods have already been optimized to analyze tiny tumor specimens.
- We use our Triple TOF 6600 (AB Sciex) mass spectrometer for the unbiased comprehensive identification of proteins that are expressed in a tumor.
- Then, we use our Qtrap 6500 (AB Sciex) and 6495 Triple Quadrupole (Agilent) mass spectrometers to develop highly sensitive and specific assays that allow us to quantify the actual levels of mutated proteins and important cancer-pathway proteins with high sensitivity and precision.
This strategy provides a unique molecular signature for each tumor, which allows us to define the actual carcinogenic drivers for each patient’s cancer in order to better guide the individualized therapy.
The Morpheus Study & Improvement of Treatment Through X-Ray
Dr. Vuong is the Director of the Segal Cancer Center’s Radiation Oncology facility at the Jewish General Hospital. She is internationally renowned in her field of research, which has benefited thousands of patients.
Dr. Vuong has seen first-hand the impact donations make in advancing cancer research and treatment.
The Morpheus Study:
Dr. Vuong initiated a pilot study called Morpheus. Participating rectal cancer patients would have required surgery to monitor a tumor that disappeared after chemotherapy and radiation therapy. Instead, endoscopy equipment was used for the study that was donated by the Jewish General Hospital Foundation. Dr. Vuong successfully monitored patients without surgery.
In the past 5 years, Dr. Vuong’s team received a mobile X-Ray unit from donors which allows patients with early breast cancer to receive intra operative radiation as a single treatment immediately post-surgery.
Some of the major advantages are:
- The reduction from 16 treatments to 1.
- Elimination of skin burns and scars on the lung.
- Better protection of the heart and ribs.
This equipment is also used to monitor patients with early rectal cancer and can be a safe cure alternative to surgery. This ultimately improves the quality of life of patients and is more efficient and cost effective.
Donations and new equipment have facilitated the improvement of cancer treatment and has currently enabled Dr. Vuong’s team to explore new treatment for patients with gynecological and skin cancer.
The Digital Droplet PCR Machine:
Improving the way cancer patients are treated and diagnosed is of the upmost importance. However, monitoring the progression and response to treatment is a crucial part of the process to recovery. This latest technology acquired by the Segal Cancer Centre supports the work accomplished in Dr. Basik’s lab.
The digital droplet PCR machine is a highly sensitive instrument that allows the detection of very small amounts of DNA released from tumor cells into the blood of cancer patients.
At the Basik laboratory, this technology is used to develop personalized assays for monitoring response to treatment and tumour progression with a simple blood test.
Dr. Nathalie Johnson: Furthering JGH’s Research Through The Ride
Dr. Johnson is the Director of the lymphoma tissue bank at the Jewish General Hospital—and she’s a Rider, too! Just like you, she’s working to give those with this disease an improved chance to fight it by furthering the research on how and why particular therapies impact lymphoma patients.
A large portion of her research focuses on particularly aggressive forms of lymphoma that target adolescents and young adults. While most lymphomas respond well to chemotherapy—some don’t. Dr. Johnson’s mission is to find out why this happens.
Patients that see Dr. Johnson are asked to participate in her research. Samples taken from patients that aren’t required for diagnostic purposes are preserved for further study. She has found that the genetic footprint is different in each cell. A blood test can now tell her more about any genetic mutation and that genetically unstable cells are more prone to die. These samples are studied to see how some patients conquer the battle while others don’t.
“The basic definition of an incurable disease is that its cells won’t die.” She believes that in some forms of lymphoma, mutated genes and their proteins have become particularly resistant to chemotherapy and inhibit its effects. The lymphoma tissue bank is central to her work. Johnson explains, “That’s why I do research, I’m comforted by the fact that my work might help the next patient.”
Money from The Ride will go specifically to fund the storage of blood from patients with lymphoma and/or other cancers treated with chemotherapy and immunotherapy. This valuable resource has been made available to multiple researchers across Quebec and Canada. It has already led to seven successful grants and multiple publications.
- To determine the best type and optimal duration of therapy in patients treated for their lymphoma. We monitor circulating tumour DNA in the blood to monitor drug response.
- To optimize effective and safe immunotherapy to cancer patients. We are a team of oncologists, hematologists, immunologists, rheumatologists and basic scientists working together to understand how to harness the power of the immune system to fight cancer, while minimizing the immune-related side-effects to patients. We accomplish this by studying the changes in the immune cells obtained from the blood of patients treated with immunotherapy.
Something Old, Something New | Integrating Chinese Medicine
What’s old is new again!
The Jewish General Hospital is continually at the cutting edge of cancer research and treatment, but in embracing a holistic approach to patient care, it also finds inspiration in practices thousands of years old.
Chinese medicine, which includes acupuncture, qigong and Chinese herbs, has become a vital part of the services offered at the Peter Brojde Lung Cancer Centre.
Each practice has been used for health and wellbeing for millenia, and as provided by Thi Tran, a physiotherapist and practitioner of traditional Chinese medicine, they offer patients an elevated level of care.
Sound Wave Superpower!
Did you know that the JGH Division of Urology is the first institution in Quebec to use image fusion to target prostate biopsy and the first in North America to treat prostate cancer patients with focal therapy using the HIFU Focal-one machine?
It is an essential tool in the active surveillance of prostate cancer and provides the improved diagnostic capabilities necessary to perform focal therapy using a High Intensity Focused Ultrasound (HIFU) Focal-one machine. This is an advanced type of targeted therapy that can effectively destroy specific areas of cancer within the prostate, while preserving normal prostate tissue and function; it is minimally invasive and has fewer side effects than surgery or radiation.
The JGH acquired the Urostation Touch mobile platform, integrating 3D applications, along with an Ultrasound machine and reusable guides, for the Division of Urology. This technology, which is used to assist prostate biopsy procedures, combines MRI and ultrasound to create a 3D image of the prostate that can more accurately locate suspicious areas and help diagnose prostate cancer.
These technologies are essential to the ongoing development of the Division’s Prostate Cancer Targeting Centre into a centre of excellence for prostate cancer diagnosis and treatment.
The Jewish General Hospital has been fortunate over the years to partner with generous donors in providing quality medical care to the people of Montreal and Quebec.
As a Canadian pioneer in robotic minimally invasive surgery, the JGH is employing its da Vinci robot to its maximum capacity. An urgent challenge at this time is to acquire a 2nd advanced da Vinci robot.
THE DA VINCI ROBOT
The current da Vinci Robot has proven immensely successful and the demand for this minimally invasive technology is growing at a pace that outstrips its availability. It is currently used for patients in such areas as Urology (e.g., removal of the prostate and kidneys, removal of tumours from the kidneys, repairs to the ureter), Cardiac Surgery (e.g., repair or replacement of the heart’s mitral valve, repair of the tricuspid valve, closure of congenital holes, removal of benign tumours on the right side of the heart), Gynecologic Oncology (e.g. removal of the uterus, removal of tumours from the ovaries, repairs to the Fallopian tubes) and General Surgery (e.g., repair of a hiatus hernia in the esophagus, removal of the gall bladder, resection of the bowel, repair of the esophagus to improve swallowing). The volume of operations performed annually at the JGH using the da Vinci robot has risen steadily from the 100 that were planned at first to close to 300 this year. In all, the Jewish General performed close to 700 operations since 2007 using the da Vinci robot.
Dr. Walter Gotlieb, who has developed an international reputation in robotic gynaecological procedures, has published widely on his research and as been appointed Chief of McGill’s Faculty of Medicine Robotic Surgery Program.
Just two years after adding robot-assisted surgery to its high-tech medical repertoire, the Jewish General Hospital (JGH) has rapidly shot to the Canadian forefront of this sophisticated field, with the most surgeons performing the greatest number of operations in the widest range of medical specialties anywhere in the country.
According to Dr. Lawrence Rosenberg, JGH Surgeon-in-Chief, ten JGH surgeons have now been trained to use the da Vinci Surgical System for a broad array of procedures in such fields as urology, gynecology, general and cardiac surgery. Robot-assisted surgery has proved to be particularly effective in treating prostate and gynecological cancers, since its use results in significantly shorter hospital stays, substantially less blood loss and a decreased risk of complications. This has prompted the Jewish General Hospital to take full advantage of the da Vinci Surgical System by performing nearly 450 operations during the past 19 months, with between four to six surgeries currently performed per week.
In robot-assisted surgery, the robotic arms—three bearing surgical instruments, and the fourth carrying a tiny threedimensional, high-definition video camera and light—are passed through small incisions and into the patient’s body. The surgeon, sitting at a special console, uses hand controls and foot pedals to manipulate all of the robotic arms with unprecedented precision and with greater flexibility than that of the human wrist.
Imagine if you walked through your front door only to discover you’d shrunk by about 1500 million times! If you stepped into your living room, you would not see chairs, tables, computers, and your family, but atoms, molecules, proteins, and cells – shrunk down to the “nanoscale.” You’d not only see the atoms that everything is made from—you’d actually be able to move them around!
Now suppose you started moving them around and sticking the atoms together in new and interesting ways. Imagine the possibilities of all the new things you could create. Everything from brand new medicines to ultra-fast computer chips. Making new things on this incredibly small scale is called “nanotechnology” and it’s one of the most exciting and fast-moving areas of science and technology today.
How is nanorobotics used in cancer treatments?
The major problem in cancer therapeutics is tumour resistance, the ability of some cells in a tumour to overcome the attack of a variety of treatments. Working with the École Polytechnique (EP) at the Université de Montreal, the Chief of Radiation Therapy at the Segal Cancer Centre, Professor Té Vuong, has embarked on a paradigm-shifting project on nanorobotics in cancer therapy.
EP Professor Sylvain Martel has discovered bacteria which essentially eat iron, which makes them magnetic. They can then be loaded with any anti-cancer agent, and in the magnetic field of an MRI, they can be actively localized into tumours. More than that, it turns out that they automatically move into the area of tumours which are low in oxygen (hypoxic), usually resistant to all treatments, including radiotherapy. The search for ‘hypoxic cell sensitizers’ has been a hunt for the Holy Grail for decades, and we appear to have found an effective approach to this major therapeutic challenge.
The nanorobotic vision:
To offer next generation treatment for patients with cancer by establishing a new hybrid program of nanorobotic guided treatment to deliver drugs targeted to tumours in conjunction with state-of-the-art radiation treatment.
The association of the Jewish General Hospital (JGH) with Polytechnique was established to innovate solutions to treatment barriers. Polytechnique is world renowned for Research and development in high technology. The JGH is a leading research centre for novel cancer treatments. The JGH and Polytechnique have been collaborating closely and well over the last four years.
This project will integrate a graduate program in oncology, bringing novel technologies to the clinics to benefits not only to Canadians but mankind.