Researchers at the Vancouver Prostate Centre in Vancouver, British Columbia, Canada, have developed a new blood test that provides unprecedented insight into a patient’s cancer make-up, potentially allowing doctors to better select treatment options that will improve patient outcomes

The technology was outlined in a study published in the July 20, 2022 issue of Nature.[1]

The first-of-its-kind blood test analyzes the DNA that metastatic cancers shed into the bloodstream, known as circulating tumor DNA or ctDNA. By sequencing the entire genome of this ctDNA, the test reveals characteristics that are unique to each patient’s cancer, giving physicians new tools to develop more personalized treatment plans.

“With only a few drops of blood, we can uncover critical information about a person’s overall disease and how best to manage their cancer,” says Alexander Wyatt, DPhil (Ph.D.) an assistant professor of urologic sciences at the University of British Columbia (UBC) and research scientist with the Vancouver Coastal Health Research Institute (VCHRI) and BC Cancer.

“This test has the potential to help clinicians choose better tailored treatment options and to more efficiently detect treatment resistance, allowing clinicians to adjust clinical care as needed,” he said.

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circulating tumour DNA
For the study, the researchers examined ctDNA samples collected from patients with metastatic prostate cancer. Metastatic cancer — cancer that has spread to other organs in the body — is not often curable, and chemotherapy and newer targeted therapies may not work for all patients. Biopsies to help determine the best treatments for this type of cancer are rarely performed due to their invasive nature and the high risk of complications. This is often a major barrier in studying and treating this disease.

Alexander Wyatt, DPhil (Ph.D.) is assistant professor of urologic sciences at the University of British Columbia and research scientist with the Vancouver Coastal Health Research Institute and BC Cancer. Photo courtesy: © 2022 University of British Columbia Faculty of Medicine. Used with permission

The researchers discovered that whole genome sequencing of ctDNA provides a host of information about the different metastases spread throughout the body. Using newly developed computer programs, the researchers were able to pinpoint the unique genetic make-up of various cancer populations in the body to gain a more comprehensive understanding of the disease.

Complexity of metastatic cancer
“Metastatic cancers are complex and our understanding of them has been limited,” Wyatt said

“Whereas traditional biopsies only provide a small snapshot of the disease, this new test is able to paint a more complete picture of metastases throughout the body, all from a simple and easy to perform blood test,” he added.

The researchers say the information can also be used to help predict which treatments will be effective or ineffective in each patient.

“Every cancer is unique and every patient responds differently to treatment,” Wyatt noted

“This new generation of ctDNA tests can help clinicians choose the treatment option that is most likely to benefit a patient,” he explained.

New insights into treatment resistance
While the number of cancer treatment options has expanded in recent years, a common problem is that eventually those treatments stop working. Drug resistance can develop over time as cancer cells accumulate molecular changes that make them less sensitive to a particular drug or treatment.

The study from Wyatt and his team sheds new light on how this resistance develops. By collecting multiple ctDNA samples over time, they were able to learn how cancer evolves in response to treatment. The findings revealed new genetic mechanisms of resistance to the most common drugs for treating metastatic prostate cancer and more broadly demonstrates how ctDNA profiling can be used to understand treatment resistance across other types of cancers.

“This technology can be applied across other types of cancer to understand how those tumours metastasize and how they eventually evade treatment,” Wyatt said.

“It will also help us design the next generation of cancer therapies that more effectively target resistant disease.”

The researchers say that this minimally-invasive, relatively inexpensive and highly-scalable technology is now being deployed across large clinical trials. This includes leading-edge precision oncology clinical trials in Canadian cancer patients being conducted at BC Cancer and the Vancouver Prostate Centre.

[1] Herberts C, Annala M, Sipola J, Ng SWS, Chen XE, Nurminen A, Korhonen OV, Munzur AD, Beja K, Schönlau E, Bernales CQ, Ritch E, Bacon JVW, Lack NA, Nykter M, Aggarwal R, Small EJ, Gleave ME; SU2C/PCF West Coast Prostate Cancer Dream Team, Quigley DA, Feng FY, Chi KN, Wyatt AW. Deep whole-genome ctDNA chronology of treatment-resistant prostate cancer. Nature. 2022 Jul 20. doi: 10.1038/s41586-022-04975-9. Epub ahead of print. PMID: 35859180.

Featured image: EDTA blood tube for CBC test in laboratory.Photo courtesy: © 2016 -2022 Fotolia/Adobe. Used with permission

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