Circulating tumour cells in melanoma

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Published: 18 May 2017
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Dr Evi Lianidou - University of Athens, Athens, Greece

Dr Lianidou speaks with ecancer at EADO 2017 about the clinical utility of melanoma patient blood samples to gain insight into disease progression and genotype.

She describes how serial blood draws can be used to gain up-to-date insight into tumour biology, disease evolution over time, and the significance of determining new and known therapeutic targets.

Dr Lianidou highlights the significance of quality control throughout the acquisition and analysis of patient samples, and introduces the Cancer-ID initiative.

ecancer's filming has been kindly supported by Amgen through the ECMS Foundation. ecancer is editorially independent and there is no influence over content.

This area is a very hot topic in cancer research at the moment. It has to do with very different aspects of finding important information in the peripheral blood of a patient with cancer, with solid cancer. It is among the ten top medical innovations of 2017, liquid biopsy.

What is liquid biopsy? Liquid biopsy is to find information and follow the tumour evolution over time through a simple blood test. That means that we get blood, peripheral blood, a simple blood test from a patient with cancer and then in this blood we can look for specific markers that give us information on the evolution of the tumour. What are these markers? These markers can be circulating tumour cells, these are the cells that are released from the primary tumour and through circulation in the blood they can get into secondary sites where they form the metastases.

So one part is this, the other part is to look for circulating tumour DNA, that is cell free DNA circulating in blood. This can also give us information on important genes for cancer. The other part is we can check for circulating microRNAs. My talk was focussed on circulating tumour cells and especially in melanoma.

In patients with solid cancers these cells circulate in the body and it’s a challenge, an analytical challenge, to try to find these cells because they are very rare. It’s like a needle in a haystack, it’s very difficult to find them and to isolate them. But after finding and isolating these cells we can actually look at them, check their biology, look at genes that are expressed on these cells and, moreover, we can follow patients over time by serial blood draws. That means we can see whether in these cells there are some markers that are important for the prognosis of the patient; there are markers that are important for the selection of patients for specific therapies. The FDA has already cleared some assays in this area for metastatic breast, colorectal and prostate cancer but not as yet for melanoma. But there are a lot of clinical studies showing the clinical importance of this analysis.

There are studies in the early setting, before and after therapy. We can detect these cells’ important alterations in genes like BRAF V600 mutation, that is important for specific drugs like vemurafenib. We can also look for important markers, like we do in my group, for PD-L1 in these cells but these studies are still ongoing. So this is an important area because as soon as the primary tumour is removed through surgery you cannot have any access to the outcome and to the clinical condition of the patients unless you do an imaging technique. For these imaging assays to see something means that you must have a lot of cells in the metastatic site. So this area of liquid biopsy is here to fill this gap, to give us information through serial blood draws.

I would say for the circulating tumour cells, and for this area in general, a very important issue is the quality control of these tests so that we are very sure that these tests should be performed in certified labs. We have to control all the conditions, the pre-analytical conditions up to the clinic, up to the final result because this result is very critical for the patient. So we must control all the conditions, the pre-analytical conditions, the stability of the sample, the time of sampling, which types of tubes you collect, how you perform the analysis, how you isolate the cells. There are a lot of technologies for the isolation of these cells so for very specific types of cancer you may need different technologies because the cells are very heterogeneous. They represent the tumour heterogeneity in many ways so it’s a different story to isolate cells in breast cancer patients and isolate cells for melanoma patients. One thing is this. So there is now a European initiative, that’s a European consortium called CANCER-ID. There are many groups all over Europe, academic groups together with pharma companies, and we are trying in this consortium to synchronise and compare different technologies so that this test can be robust and can enter routine clinical use. At the same time in the US there is a big consortium as well, it’s called the Cancer Moonshot Programme where liquid biopsy plays also a very significant role.