Cultured CTCs reveal genetic profile and potential drug susceptibility of breast cancer cells

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cancer cells 3d oncology news australia_800x500US scientists have developed an improved method of collecting and growing rogue cancer cells from blood samples.

The discovery could help study how tumours evolve, and understand how their genes change over time. This in turn may help guide research into new treatments.

Cancer drugs can become ineffective as tumours acquire new genetic faults over time, so a major challenge in cancer therapy is combatting this drug resistance.

At present, samples are taken from patients’ tumours – a biopsy – for analysis. But biopsies are invasive and can be uncomfortable for patients. On top of this, the material collected from biopsies may only allow a limited amount of analysis, providing a single snapshot in a tumour’s genetic history.

In a study, published in the journal Science, experts from the Massachusetts General Hospital (MGH) Cancer Center looked at ways of collecting small numbers of cancer cells that are naturally shed from tumours into the bloodstream.

Once these circulating tumour cells (CTCs) are collected, they can be grown in a laboratory to help track changing genetic patterns over time. If developed into a method that can be used routinely in hospitals, this information could be used by doctors to help select the most appropriate treatment for patients.

MGH’s Professor Daniel Haber, an author on the latest study, said: “This approach of culturing circulating cancer cells in the blood, analysing them for new mutations that have developed during therapy, and testing the utility of drugs targeting those mutations could become the essence of individually adjusted cancer therapy in the future.”

But a stumbling block in the development of this approach has been successfully isolating a pure sample of tumour cells from the blood and keeping them growing in the lab.

The latest study has taken some important first steps towards tackling this challenge. The researchers used a device developed by engineers at MGH called a ‘CTC-iChip’. This can remove white blood cells from a blood sample and leave viable tumour cells behind.

The team used the device to isolate CTCs from six patients with a type of breast cancer known as ‘oestrogen receptor-positive’ breast cancer and successfully grew the cells in the lab, establishing what are known as ‘cells lines’ for subsequent analysis.

Researchers were able to screen the CTC-derived cell lines for genetic changes in hundreds of cancer-associated genes.

And in addition to the key genetic faults that had been identified in initial biopsy samples, the CTC cell lines revealed genetic changes that had been acquired over the course of treatment.

Although these early results are promising, the researchers stressed that the technology must be refined in future studies.

Dr Shyamala Maheswaran, from the MGH cancer center and an author on the study, said: “We need to improve culture techniques before this is ready for clinical use, and we are working on doing that right now.”

Cancer Research UK’s Professor Carlos Caldas, an expert in breast cancer genetics, welcomed the latest study and echoed the need to refine the approach, which is similar to his team’s own research on so called ‘liquid biopsies’.

“Fishing for genetic markers in patients’ blood samples, and using them to plot a tumour’s evolutionary history is an exciting area of research. And this latest study, focusing on rogue tumour cells in blood, is an interesting proof-of-concept in the development of these ‘liquid biopsies’. But the technology needs to be made more efficient, so that cells can be isolated from every blood sample, before this could be used routinely in hospitals.

“My team, along with other Cancer Research UK scientists, are also investigating this approach, focusing on small pieces of tumour DNA that can be isolated from blood samples, but also looking at circulating tumour cells.”

Source: CRUK/MGH


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