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New blood test uses circulating tumor DNA to help develop personalized cancer treatments

A novel blood test developed at the Vancouver Prostate Center utilizes the DNA of metastatic cancer to help with developing patient-specific treatment plans.

DNA from malignant cells and tumors is known as circulating tumor DNA (ctDNA). DNA is mostly found in a cell’s nucleus, but when a tumor grows and damaged cells are replaced by new ones, this DNA is released into the blood along with other components of the decomposing dead cells.

In a new study, researchers assessed the ctDNA of 33 patients with treatment-resistant metastatic prostate cancer. Using a novel blood test, the researchers examined the patient’s ctDNA, and identified the unique attributes of each patient’s cancer. Using whole genome sequencing of ctDNA, the test will provide doctors with additional resources to create more individualized treatment regimens.

The authors stated, “serial ctDNA sampling presents new opportunities, as the increased data dimensionality allows resolution of previously ambiguous scenarios.”

Due to their invasive nature and significant complication risk, tissue biopsies are seldom carried out to establish the best therapy for metastatic prostate cancer. This is frequently a big obstacle to understanding and treating this illness.

The research team found that the whole genome sequencing (WGS) of ctDNA yields a wealth of data regarding the metastases (cancerous tumors) dispersed throughout the body. Using a newly developed computer software program, the team was able to identify the distinct genetic make-up of the body’s different cancer populations.

Dr. Alexander Wyatt, one of the authors of the paper, told UBC news, “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.”

The study suggests that the new blood test can be used as a tool for providing a more comprehensive understanding of the cancer characteristics of various cancer types.

Dr. Wyatt concluded by saying, “This technology can be applied across other types of cancer to understand how those tumours metastasize and how they eventually evade treatment. It will also help us design the next generation of cancer therapies that more effectively target resistant disease.”

The study was published in Nature on July 20th, 2022.

Abstract. Circulating tumour DNA (ctDNA) in blood plasma is an emerging tool for clinical cancer genotyping and longitudinal disease monitoring. However, owing to past emphasis on targeted and low-resolution profiling approaches, our understanding of the distinct populations that comprise bulk ctDNA is incomplete. Here we perform deep whole-genome sequencing of serial plasma and synchronous metastases in patients with aggressive prostate cancer. We comprehensively assess all classes of genomic alterations and show that ctDNA contains multiple dominant populations, the evolutionary histories of which frequently indicate whole-genome doubling and shifts in mutational processes. Although tissue and ctDNA showed concordant clonally expanded cancer driver alterations, most individual metastases contributed only a minor share of total ctDNA. By comparing serial ctDNA before and after clinical progression on potent inhibitors of the androgen receptor (AR) pathway, we reveal population restructuring converging solely on AR augmentation as the dominant genomic driver of acquired treatment resistance. Finally, we leverage nucleosome footprints in ctDNA to infer mRNA expression in synchronously biopsied metastases, including treatment-induced changes in AR transcription factor signalling activity. Our results provide insights into cancer biology and show that liquid biopsy can be used as a tool for comprehensive multi-omic discovery.

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.

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