Learning How to Fly Blind

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New approach can detect cancer in different patients without the need for tumour biopsies.
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Blood contains a vast array of components. In addition to blood cells, plasma and proteins, are free-floating pieces of DNA—some of which can originate from cancer cells and are known as circulating tumour DNA.

Recent findings published in Clinical Cancer Research highlight a new approach to detect cancer in blood samples—opening up new possibilities for using blood-based tests to diagnose and monitor individuals with cancer.

The approach was developed by a multidisciplinary team that included researchers at the University Health Network, the University of Toronto and the Vector Institute. It was led by Drs. Scott Bratman and Daniel De Carvalho, Senior Scientists at the Princess Margaret Cancer Centre, and their graduate student Justin Burgener.

The strategy involved an integration of methods that analyzed different molecular features. The researchers performed in-depth sequencing on the free-floating DNA present in the blood to identify mutations specific to tumours. In addition to identifying these genetic features, the team measured modifications to that DNA—known as epigenetic changes—and analyzed the lengths of the DNA fragments, which provided rich multi-dimensional data. Also, to refine the data, DNA mutations and epigenetic changes found in white blood cells present in each sample, as well as blood from healthy individuals, were used to remove unwanted background noise.

“This integrated approach is unique and advances our ability to identify clinically relevant biomarkers for a wide variety of cancer types,” says Dr. Bratman.

The researchers chose to test the strategy in early stage squamous cell carcinoma, the most common type of head and neck cancer. Choosing this ‘localized’ type of cancer enabled the team to confirm that the blood test works for cancers that are located at single sites in the body, and before they begin to spread. It also verifies whether this test can be used when there are low amounts of free-floating DNA derived from tumours in the blood.

The researchers analyzed blood samples from 30 individuals with squamous cell carcinoma as well as blood samples from 20 healthy individuals. By comparing the rich sequence and epigenetic data between cancer and healthy samples, as well as with an existing sequence database known as The Cancer Genome Atlas, the researchers we were able to identify markers in the blood that could be used to predict clinical outcome and, potentially in the future, guide therapies.

“Doctors need better ways of detecting cancer and then monitoring treatment response without relying on tumour biopsies. Because our method can be applied across cancer types even when tumour tissue is not available for molecular analysis, it addresses a key limitation of current tests and provides new avenues for future research,” says Dr. De Carvalho.

Supported by the Gattuso-Slaight Personalized Cancer Medicine Fund at the Princess Margaret Cancer Centre; the Strategic Training in Transdisciplinary Radiation Science for the 21st Century (STARS21) training program; the Canadian Institutes of Health Research; the Ontario Institute for Cancer Research; the Province of Ontario; The Princess Margaret Cancer Foundation; the Conquer Cancer Foundation (American Society of Clinical Oncology); and the Princess Margaret Cancer Centre Head & Neck Translational Program, which is supported by philanthropic funds from the Wharton Family, Joe’s Team, Gordon Tozer and the Reed Fund. DD De Carvalho is a Tier 2 Canada Research Chair in Cancer Epigenetics and Epigenetic Therapy.

Burgener, JM, Zou J, Zhao Z, Zheng Y, Shen SY, Huang SH, Keshavarzi S, Xu W, Liu F-F, Liu G, Waldron JN, Weinreb I, Spreafico A, Siu LL, de Almeida JR, Goldstein DP, Hoffman MM, De Carvalho DD, Bratman SV. Tumor-naïve Multimodal Profiling of Circulating Tumor DNA in Head and Neck Squamous Cell Carcinoma. Clin Can Res. 22 June 2021. doi: 10.1158/1078-0432.CCR-21-011

Dr. Scott Bratman is a Senior Scientist at the Princess Margaret Cancer Center and co-senior author of the study.

(L) Graduate student and first author of the study, Justin Burgener; and (R) co-senior author Dr. Daniel De Carvalho, Senior Scientist at the Princess Margaret Cancer Centre.