In the blood:
Detecting and treating cancer earlier with liquid biopsies

In a recent episode of the Genetics Unzipped podcast, Susan Galbraith, Executive Vice President, Oncology R&D at AstraZeneca, discusses how liquid biopsy is enabling the detection and treatment of cancer, together with Professor Charles Swanton from the Francis Crick Institute and Sir Harpal Kumar, President of GRAIL Europe.



Imagine if a small blood sample could tell you everything you want to know about the presence and origin of cancer within the body, to help clinicians select the best treatment for patients and then monitor how well it is working.

This idea is fast becoming a reality thanks to advances in technology that enable the detection of tiny fragments of DNA shed into the bloodstream from cancer cells, known as circulating tumour DNA (ctDNA).1 As a consequence of this innovation, the use of ‘liquid biopsy’ is moving from the arena of research into clinical practice.2

Revealing the secrets in ctDNA to inform treatment strategies

Most cells release DNA into the bloodstream as they are damaged, dying or dead, and cancer cells are no exception.3 Through the use of technologies such as next-generation sequencing,4 these fragments of DNA can reveal a wealth of information about cancer, without the need for invasive surgical biopsies. At a basic level, ctDNA can reveal information about the likely presence and burden of cancer within the body. But our abilities now go much further. Detecting the presence of particular genetic mutations in ctDNA can provide vital insights to inform the optimal treatment for each patient.

Furthermore, analysing the frequency of mutation events sheds light on the evolution and heterogeneity of tumours. We can now start to see which mutations are likely to be shared by all cancer cells and which are shared by a smaller proportion of cells, with significant implications for the emergence of resistance to therapy and the eventual return of the disease.5

Beyond changes to the genetic code, we now can study patterns of DNA methylation on ctDNA - molecular tags that can alter the expression of genes, also known as epigenetics. These alterations reveal important clues about the likely tissue of origin and behaviour of cancer, further informing the most appropriate diagnostic and therapeutic strategy.6

Putting this into practice, ctDNA can potentially help doctors identify which patients are most likely to benefit from a particular treatment regimen. It can also be used to monitor the ongoing response to therapy with greater sensitivity and speed than typical imaging scans, allowing doctors to switch treatments sooner if necessary.7


Discover how we are leveraging circulating tumour DNA to uncover new insights on cancer detection and treatments in the below video:

Improving outcomes through early detection

Not only does liquid biopsy technology have the potential to improve treatment for people who have already been diagnosed with cancer, but also researchers are exploring the potential to use ctDNA for early detection and screening.8

For example, our collaborators at GRAIL have developed a multi-cancer blood test based on DNA methylation patterns in ctDNA.9

We are particularly excited to explore the possibilities of GRAIL’s technology to enable the identification and treatment of cancer at an earlier stage when treatment is likely to be even more effective and the chances of survival are higher.10 This allows us to move drugs that are currently being trialled in the late stages of cancer into the early stages of the disease more rapidly than we've ever done before, helping us to build more effective treatment regimens.11

We believe liquid biopsy technology and ctDNA analysis are set to transform cancer care, from the earliest stages of screening and diagnosis through treatment to long-term follow-up, which means the potential for significantly improved outcomes from where we are today.




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References:

  1. Cheng F et al. Circulating tumor DNA: a promising biomarker in the liquid biopsy of cancer. Oncotarget. 2016; 7(30): 48832-48841.
  2. Siravegna G et al. How liquid biopsies can change clinical practice in oncology. Annals of Oncology. 2019; 30(10):1580-1590.
  3. Institute for Quality and Efficiency in Health Care (IQWiG). How do cancer cells grow and spread? National Library of Medicine - PubMed Health. September 2016.
  4. Zhong Y et al. Application of Next Generation Sequencing in Laboratory Medicine. Ann Lab Med. 2021;41(1): 25-43.
  5. Fisher R et al. Cancer heterogeneity: implications for targeted therapeutics. Br J Cancer. 2013; 108(3): 479-485. 
  6. Herceg Z & Hainaut P. Genetic and epigenetic alterations as biomarkers for cancer detection, diagnosis and prognosis. Mol Oncol. 2007; 1(1): 26-41.
  7. Weaver C H. Ask The Experts About Circulating Tumor DNA in the Management of Cancer. Cancer Connect. April 2022. Accessed on 7 June 2022 from https://news.cancerconnect.com/colon-cancer/ask-the-experts-about-circulating-tumor-dna-in-the-management-of-cancer
  8. Fiala C and Diamandis E P. Utility of circulating tumor DNA in cancer diagnostics with emphasis on early detection. BMC Medicine. 2018;16:166.
  9. Ofman J et al. GRAIL and the quest for earlier multi-cancer detection. Nature Portfolio. Accessed on 7 June 2022 from https://www.nature.com/articles/d42473-020-00079-y
  10. Galleri. Early Cancer Detection: How to Find Cancer Early. Accessed on 30 June 2022 from https://www.galleri.com/multi-cancer-early-detection
  11. GRAIL. (2022, June 2). GRAIL Announces Strategic Collaboration with AstraZeneca to Develop Companion Diagnostic Tests to Enable the Treatment of Early-Stage Cancer [press release]. Retrieved from https://grail.com/press-releases/grail-announces-strategic-collaboration-with-astrazeneca-to-develop-companion-diagnostic-tests-to-enable-the-treatment-of-early-stage-cancer/

Veeva ID: Z4-66887
Date of preparation: July 2024