How precision medicine can improve early cancer detection and interception

By Dr. Nicole Beauchemin* 

Most of us who have experienced cancer personally or have had a loved one go through a cancer diagnosis are intimately aware of the power of early cancer detection. We know, better than most, that the sentence “good thing we caught it early” will likely indicate a positive prognosis. 

Cancer survival statistics reinforce this concept. In Canada, 90 per cent of people diagnosed with cancer at its earliest stage (Stage I), survive at least five years after diagnosis.  On the other hand, when a cancer is diagnosed at Stage IV, this number drops to less than 20 per cent. And even for those in this last group who do survive past the five-year mark, treatments seldom lead to full life-long remission, thus requiring follow-ups and elevating chances of undergoing multiple treatments. The physical, emotional and psychological costs of late diagnosis to patients and their families are enormous. In addition, the economic costs to our healthcare systems are presently (and will continue to be) difficult to sustain. 

In this context, it is imperative to find better ways to detect – and intercept – cancers at early stages. 

Methods of cancer detection 

Biochemical and imaging tests have been used to detect cancer in early stages for more than 75 years. These methods have been validated through large clinical trials and continue to be used effectively in the clinic.   

Some examples of biochemical tests include elevated Prostate-Specific Antigen (PSA), Carcinoembryonic Antigen (CEA) and CA125 antigen, which can be used to identify cases of suspected prostate cancer, advanced colorectal and ovarian cancers, respectively.  Fecal occult blood tests (i.e. tests used to check stool samples for blood) and colonoscopies are routinely used to detect colorectal cancers. Imaging technologies can also detect certain cancer types, such as mammography for breast cancer or digital X-Rays, MRI and CT scans and ultrasounds for lung and pancreatic cancers. 

Although these biochemical and imaging tests are good at detecting early-stage cancers, they can be cumbersome and expensive to apply. Identifying populations at higher risk of developing cancer has therefore helped focus screening efforts on those most likely to benefit. 

Much research has gone into identifying cancer risk factors. For example, a better understanding of the roles of smoking, viral hepatitis C infections (which play an important role in liver cancer) and HPV infections (which is the main risk factor for cervical cancer) has led to the creation of targeted screening protocols that are helping to identify more early-stage cancers. 

Breakthroughs in genomic sciences over the last two decades have opened new avenues to identify at-risk populations. For example, we now know that mutations in genes such as BRCA1, BRCA2, CHEK2 and PALB2 increase the risk of developing breast, colorectal and/or pancreatic cancers. Screening protocols applied to individuals who carry such mutations can therefore enhance early detection. The same is true for individuals with specific mutations in the MLH1, MSH2, MSH6, PMS2, or EPCAM genes that are associated with a cancer condition called Lynch Syndrome, or those with mutations in the TP53 gene, which can lead to a cancer predisposition syndrome called Li-Fraumeni Syndrome.  

More recent genomic innovations have the potential to revolutionize both the accessibility and accuracy of screening methods. For example, a recent study led by researchers at the Princess Margaret Cancer Centre in Toronto showed that searching for small pieces of tumour DNA in the blood of individuals with Li-Fraumeni Syndrome (an approach sometimes called "liquid biopsies") can be used to detect cancers earlier than conventional screening methods. Although such a test will need more validation before being applied widely in the clinic, these promising technologies provide exciting opportunities to further improve early detection. 

Strategies for early interception 

Genomics has not only been a crucial piece of the puzzle when it comes to improving early detection, it is also an important factor in the development of treatments tailored to cancers that are caught early. This is where precision medicine comes in.   

Precision oncology, or precision medicine for cancer, seeks to provide the right treatment at the right time for each patient, based on the genetic and biological characteristics of their individual cancers. For this to happen, DNA (and sometimes RNA) from a patient’s blood and tumour are sequenced, revealing inherited or acquired mutations that may be causing their cancer. In some cases, this knowledge can be used to provide patients with the treatment that is most likely to be effective against their cancer. 

The Marathon of Hope Cancer Centres Network (MOHCCN) is a novel pan-Canadian initiative seeking to improve cancer treatments by bringing together cancer researchers, clinicians, patients, and administrators across the country to accelerate research into precision oncology. The Network is collecting molecular data from thousands of patients and linking it with clinical data, including treatment responses. This dataset promises to be the largest and most complete cancer case resource ever generated in Canada, and will have few parallels across the world.  

This rich resource will provide valuable information about all stages of cancer, including new insights into the biology of early tumours. This knowledge can potentially be leveraged to identify cancer-specific proteins at different stages of tumour growth – including in very early phases – revealing novel therapeutic targets and giving rise to powerful treatments that can be applied early after cancer detection.  Similarly, the molecular tools developed through this initiative may also be used to reveal biomarkers indicating disease progression or regression. These exciting research developments are instilling hope to cancer patients and their families and are demonstrating promise for more effective interception early in cancer development, possibly extending survival and promising a better quality of life for cancer patients.   

Beyond early detection and interception 

Many challenges will need to be overcome to better detect and treat all cancers earlier, and precision oncology will be a key part of surmounting them. These challenges include better understanding of the biology of early tumours, developing appropriate models of early disease to test new drugs specific for this stage, enhancing statistical and risk models able to identify at-risk individuals or populations, and creating new computational tools to integrate all the data identified by diagnostics and produced in large clinical trials.

Addressing these challenges is part of the mandate of the MOHCCN. The project is supporting innovative techniques to improve screening and detect and target tumours earlier, and the comprehensive and high-quality data generated and shared through the Network will further accelerate research in this field in Canada and across the world. Enhanced cooperation in research and clinical operations between Canadian cancer centres through the MOHCCN will also ensure that new approaches can be implemented rapidly across the country. 

These new initiatives are already leading to better methods for early cancer detection and intervention, which promise to improve outcomes and quality of life for cancer patients while also reducing the financial burden of cancer on our healthcare systems.  Still, we must not forget that cancer prevention on a population-wide level is still the gold standard for reaching these goals. Using enhanced education campaigns highlighting how an active lifestyle, appropriate diet interventions diminishing sugars, fat, salt and alcohol/drug consumption, and alleviation of stress-induced conditions can greatly reduce cancer rates.   

Not all cancers are preventable, however. For those who will develop cancer, early detection and availability of novel precision oncology-based biomarkers and treatments will undoubtedly provide hope for better outcomes and quality of life. 

*Dr. Nicole Beauchemin is a 23-year cancer survivor. She is also a researcher and emerita professor at McGill University’s Gerald Bronfman Department of Oncology, as well as in the Departments of Biochemistry and Medicine. She is also a member of the Goodman Cancer Institute. She currently serves as co-chair of the Marathon of Hope Cancer Centres Network’s Patient Working Group.