'Liquid' lung cancer biopsies will speed up drug resistance research

Cancer Research UK

Analysing cancer cells from a lung cancer patient’s blood sample could help monitor and predict their response to treatment, according to a new study from scientists in Manchester.

“This latest research should accelerate progress by helping us understand why certain patients stop responding to drugs" - Professor Charlie Swanton, Cancer Research UK

The finding will speed up research into new therapies, and improve the understanding of how tumours become resistant to drugs, experts said.

The new research looked at blood samples from six patients with a form of the disease called small-cell lung cancer (SCLC), “a devastating disease, where treatments often work initially, but then the tumour develops resistance and carries on growing," said Cancer Research UK's Professor Charlie Swanton, who was not involved with the research, but who works on a large UK lung cancer study, called TRACERx that is looking at how lung cancers evolve over time.

"We’re only just beginning to understand how tumours do this. As a result, survival rates have barely improved over the last forty years".

The slow progress has been, in part, because understanding how resistance develops has been hampered by researchers' inability to track the disease over time, Professor Swanton added. 

One key technical hurdle is that a traditional tissue sample - or biopsy - contains a limited amount of tumour cells.

"Access to sufficient tumour tissue is a major barrier to us fully understanding the biology of SCLC," says Professor Caroline Dive at Cancer Research UK’s Manchester Institute – part of the Manchester Cancer Research Centre - who led the new study.

To try to tackle this problem, her team have been studying the potential of using circulating tumour cells (CTCs) – cells that have broken off from the tumour and are circulating in the blood – to monitor a patient’s disease without needing a biopsy.

In their new study, published in the journal Nature Medicine, Professor Dive's team, working with lung specialists at The Christie NHS Foundation Trust, found that blood samples from patients with SCLC had many more circulating tumour cells in them than did samples from patients with other types of cancer.

They discovered that the number of CTCs in each SCLC patient's sample was related to their survival – patients with fewer tumour cells in their blood lived longer.

In addition, the team were able to use cells extracted from a patient’s blood to study their disease in mice. When they treated these mice with the same chemotherapy drugs as the patients, the mice responded in the same way as each donor patient.

"This liquid biopsy is straightforward and not invasive, so can be easily repeated and will allow us to study the genetics of each lung cancer patient’s individual tumour," said Professor Dive.

"It also means that we may have a feasible way of monitoring patient response to therapy, hopefully allowing us to personalise and tailor individual treatment plans to each patient.

“We can use these models to help us understand why so many SCLC patients acquire resistance to chemotherapy, and to search for and test potential new targeted treatments,” added Professor Dive.

According to Professor Swanton, the new finding will accelerate research by allowing scientists to understand why certain patients stop responding to drugs.

"This will allow us to develop new ways to diagnose and treat this disease – ultimately improving survival for patients with small cell lung cancer,” he added.

References

  • ​​​Hodgkinson C.L, et al. (2014). Tumorigenicity and genetic profiling of circulating tumor cells in small-cell lung cancer., Nature medicine, PMID: