Prostate cancer biomarker identification and treatment improvement through analysing and monitoring circulating tumour cells

The recent advances in genetic/molecular characterisation of cancer cells and the development of specific therapies based on those genetic/molecular changes has paved a new efficient way for cancer patient treatment, termed ‘personalised medicine’ which is based on each individual’s cancer genetic/molecular makeup. The genetic alternations in cancer cells change progressively as the cancer advances and in response to therapy. They need to be frequently monitored to select the best treatment at different disease progression time-points. In practical terms, this is difficult using tissue biopsies, which are currently the routine cancer diagnosis method, due to their invasive nature and cost. Cancer cells can migrate into blood vessels where they are carried by the circulation to establish cancers, called metastases, at different sites in the body. Even before a metastatic tumour is clinically evident, a large number of cancer cells already exist in the blood, called circulating tumour cells (CTCs). CTC analysis requires only a blood sample, easily repeated, allowing frequent molecular/genetic analysis during disease progression and treatment to select the best treatment in a cost-effective, minimally invasive and timely manner.

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Recently, a number of devices have been developed to capture the CTCs,
which are a rare population of cells in the blood. The CellSearch system has been approved by the US Food and Drug Adminstration (FDA) for clinical use in counting CTCS. To date, CTC counting has been included as a biomarker in more than four hundred clinical trials. In this clinical trial of chemotherapy for prostate cancer, CTCs, but not prostate specific antigen, rapidly predicts which patients would benefit from treatment. The researchers have recently optimized one CTC isolation device, the Parsortix system, which captures CTCs based on the much larger size of cancer cells than the blood cells. Using Parsortix, the researcher capture those CTCs with high metastasis features. Furthermore, they have developed novel genetic/molecular techniques for CTC analysis, including a technique that enables the analysis of multiple genomic changes in individual CCs for the first time.

img_5306This study is the first phase of a three year project, led by Dr Yong Jie Lu in which researchers will perform novel genetic analysis of CTCs isolated using Parsortix from around 200 prostate cancer patient samples. During the year long study, researchers plan to collect sixty patient samples for CTC analysis in order to evaluate the benefit of using these novel CTC analysis techniques for stratifying prostate cancer patient treatment. A number of genetic changes will be detected in CTCs. Correlating these genomic changes with the clinical data, researcher hope to identify certain genetic alterations associated with chemotherapeutic response, which can be determined in a future in a blood sample before and/or during the treatment to inform the best treatment required for each patient.

Cancer patients mainly die from the metastasis and CRCs are associated with cancer metastasis. These genetic analyses of CTCs will also help us to understand cancer metastasis. Thus, this novel approach will accelerate the clinical application of blood sample based molecular diagnosis, which will be much safer, more convenient, cost efficient and acceptable to patients and clinicians alike than tissue based diagnosis. It is hoped that it will significantly improve patient management and outcome.

The most common male cancer in Western countries is prostate cancer. Currently, the cancer diagnosis, prognosis and treatment decisions are heavily reliant on pathologically examinations of the cancer cells using biopsy tissue. However, a biopsy is an invasive procedure and cannot be carried out on patients regularly. Most treatment decisions are based on the tissue analysis performed a long time ago. The cancer keeps on progressing with accumulation of genetic changes overtime. Therefore it is important to analyse patient cancer cells regularly to monitor cancer progression and give the most efficient type of treatment at the right time. CTCs can be detected in patient’s blood samples, making it possible to regularly analyse patients cancer cells in order to monitor disease progress and give the correct treatment accordingly.

The key targets of the study are:img_5311

  • To collect sixty prostate cancer patient blood samples and isolate CTCs.
  • To genetically prove that cells with cancer metastasis morphological features are cancer cells.
  • To investigate the association between CTC number and clinical information
  • To generate a panel of genes, whose alterations  correlate with poor prognosis and chemo-resistance (in the long term three year project).

 

So far the researchers:

  • Have collected more than one hundred blood samples  from 25 prostate cancer patients before and during chemotherapy and CTCs isolated.
  • CTCs have been identified from the above samples by staining different types of CTC morphological markers with different colours.
  • Five rounds of genomic tests were applied to each of the thir
    teen CTC samples to correlate the genomic changes with the morphological markers. This analysis confirms from the genomic feature that the cells with different cancer cell morphological markers are CTCs.

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  • Preliminary CTC analysis based on current CTC samples shows the correlation of CTC number and aggressiveness of the cancer, and AR gene change is associated with hormone therapy resistance. More samples need to be analysed for chemo response analysis.

Currently there are deficiencies of current prognosis for prostate cancer. But this research offers a solution in the form of combining CTCs with traditional tests which can provide mor
e reliable results. Furthermore, a biopsy is an invasive and expensive test. Conversely, CTCs can be obtained by a simple blood test to monitor the cancer in real time and contribute to personalized treatment. Genetic studies and drug test can be performed on CTCs, which can help us better understand prostate cancer and allow us to provide better treatment for those affected by prostate cancer.

Last Reviewed 4/6/2018. Next review December 2018

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