SINGAPORE, Dec. 1, 2015 /PRNewswire/ -- Scientists from the National University of Singapore (NUS) have developed a novel technique to efficiently culture clusters containing circulating tumour cells (CTCs) in 14 days that could be used to predict the outcome of cancer treatment and monitor the status of cancer. Using the technique, the team achieved a success rate of more than 60 per cent in culturing CTCs from patients with metastatic breast cancer, the highest known success record to-date. This breakthrough brings researchers a step closer towards enabling personalized cancer treatment and monitoring.
A paper describing the collaborative work conducted by scientists from the Mechanobiology Institute, Singapore (MBI) and Cancer Science Institute of Singapore (CSI) at NUS, together with the National University Cancer Institute, Singapore (NCIS), was published in the medical journal Oncotarget (2015).
CTCs are 'runaway' cancer cells that escape from primary or secondary tumours. They circulate in the bloodstream and eventually invade into other parts of the body where they establish metastasis. CTCs can be found even at early stages of the disease.
However, CTCs comprise many sub-populations and occur at extremely low frequencies in blood. The chance of getting CTCs in a blood sample is akin to trying to find a hundred people in a world of seven billion people. Owing to this rarity, the population of CTCs needs to be expanded before they can be used for clinical analysis.
Professor Lim Chwee Teck from MBI, one of the study's lead authors, explained, "Being able to capture CTCs and grow them efficiently from a blood sample is a big step forward in liquid biopsy for tumour diagnosis and cancer treatment monitoring. This could potentially mean that biopsy for cancer diagnosis and prognosis could be done using a blood test, which is minimally invasive, instead of having to remove cells from the tumour itself. Results of the tests on these CTCs could help doctors assess the best therapy options for a patient, and frequent blood tests can also be done during the course of an anti-cancer treatment to provide real-time monitoring of a patient's progress during treatment."
Dr Lee Soo Chin from NCIS and CSI, the study's clinical lead, added, "Tests can potentially be done on the cultured CTCs to guide the selection of drug therapy. Cultured CTCs of individual patients can be tested for drug sensitivity to determine the responsiveness of the CTCs to the drugs used in the cancer treatment. This could allow doctors to decide on the most suitable drug for the patient based on the drug sensitivity results. As the CTCs can be cultured in a short time period, the entire testing process can take as short as four weeks – two weeks for culturing the CTCs and two weeks for drug screening. Patients will not have to wait a long time for the test results."
Currently, most methods used to culture CTCs have either lacked efficiency or required pre-selection techniques for the elimination of non-cancerous cells that led to the damage and loss of some CTCs in the process.
In an attempt to overcome these setbacks, NUS scientists developed a novel methodology to efficiently culture clusters containing CTCs from blood samples. They created an ideal environment – using a combination of specially designed microwells and oxygen-deficient growth conditions – for tumour cells to grow while other non-cancerous cells gradually undergo cell death.
The team has been able to obtain cultures from screening of samples from some early-stage breast cancer patients. Analysing patients' blood for CTCs may have potential applications in predicting patient progression or response to cancer treatment.
Said Dr Lee, "Half of these early-stage breast cancer patients have been found to have CTCs in the culture after surgery and post-operative chemotherapy, despite them not having cancer that can be detected using conventional means such as scans and who are presumed cured. We will need to continue tracking these patients to determine if the persistence of these CTCs is associated with early cancer relapse."
Tests were conducted on 226 clinical blood samples obtained from 92 metastatic or early-stage breast cancer patients who began anti-cancer therapy, and a success rate of over 60 per cent in culturing clusters containing CTCs was achieved using the novel technique, more than two to three times higher than conventional methods of culturing CTCs.
The team is also currently developing new technologies for liquid biopsies that will allow them to perform single cell analysis, so that each and every cell taken from the biopsy can be examined closely to obtain critical information that will be useful to scientists and clinicians to better treat cancer. Liquid biopsy, at present, is to do a number count of CTCs to correlate with the severity of the cancer and track treatment outcomes.
Prof Lim is also looking forward to embark on research to develop novel technologies that can contribute towards personalised or precision medicine. He said, "Cancer is extremely difficult to treat due to presence of many sub-varieties of cancer cells, which may also further mutate and change. The genetic makeup and immune response of each individual can also result in very different outcomes despite receiving the same treatment. The 'one size fits all' approach has proven to be ineffective and only individual patient-derived information can help us do a better job. We are looking at developing technologies that can acquire such critical information so that clinicians can tailor and administer precise treatment for each individual patient."