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Liquid biopsies and their promise for pancreatic cancer

We’re keen to support early career researchers who have chosen to focus on pancreatic cancer, such as PhD student Lavanya Sivapalan from Queen Mary University of London, who carries out innovative research into liquid biopsies.

We invited Lavanya to present her research at our Supporters Conference in 2019 and thought we’d share an overview of her fascinating presentation with you.

Researchers need to understand the precise genetic make-up of the tumour to develop new drugs that can help. A standard biopsy – taking a small tissue sample from the tumour, then analysing it – is the accepted procedure, but it is invasive and often uncomfortable. It is also particularly difficult with pancreatic cancer because the pancreas is situated deep inside the body.

With the advent of more powerful and sensitive instruments, researchers can now generate the same information about tumours by analysing tiny fragments of DNA that break free from a tumour and enter the bloodstream, known as ‘circulating tumour DNA’ or ctDNA. Analysing these DNA fragments found in blood samples is known as a liquid biopsy.

Lavanya’s particular interest is in studying a series of blood samples from patients that are collected at different time points throughout the course of their illness. These samples are donated by patients to the tissue bank at Barts Cancer Institute.

She explains: “We use machines known as ‘next generation sequencers’ which can decode each molecule of tumour DNA within a blood sample to reveal errors, or mutations, in the order of the chemical bases that make up each strand. Using this method, we can reconstruct the patterns of mutations within each patient blood sample, and in doing so, map the genetic profile of each patient’s tumour at the time the sample was taken.

“This information allows us to track changes in patients’ tumours over time, which is exciting because it can not only help us to identify and understand the genetic changes that happen within tumours as they grow, but it can also – crucially –monitor what effect treatment is having in that patient.

“For example, if there are signs of tumour DNA in the blood after treatment or surgery, it may indicate the cancer has come back. Or, if new genetic changes are seen during treatment, then that patient may benefit from switching to a different treatment that targets the cancer’s newly acquired changes.”

For pancreatic cancer in particular, where prompt treatment can make a big difference in prognosis, liquid biopsies also hold huge promise: “Our early work has shown that these ‘genetic signatures’ can be detected in the blood months before they can be seen in a clinical setting,” says Lavanya.

Lavanya is now working on cataloguing the most common mutations found in circulating pancreatic tumour DNA. This could also help speed up the treatment response monitoring process, because knowing which regions of DNA sequences are likely to contain new mutations gives researchers a head start by narrowing down where they should look first.

Despite working in this field for four years it was the first time Lavanya had met people directly affected by pancreatic cancer – and the experience proved to be hugely rewarding.

She told us:
“As a PhD student, this was the first time I have had the opportunity to speak to so many people whose lives have been touched by this disease. It was truly inspiring to hear them share their personal experiences and humbling to see their determination to ensure others don’t go through the same experiences as their loved ones. It has certainly reaffirmed my decision to continue to pursue pancreatic cancer research in my future career, and the whole day has definitely been a highlight of my PhD so far.”

Lavanya’s PhD studies are supervised by Professors Hemant Kocher and Claude Chelala, who lead the PCRF-funded National Pancreas Tissue Bank at Barts Cancer Institute, Queen Mary University of London.