Novel liquid biopsy platform

news
12 May 2015

Thomas Jefferson University has entered into a partnership with Exosome Sciences Inc. to evaluate a novel liquid biopsy platform that might offer clinicians new and actionable information about a patient's cancer as the disease progresses and changes via a simple blood test.

"The term 'liquid biopsy' describes the fact that a simple blood sample can contain many tumour-derived molecules and even tumour cells enabling molecular analyses similar to those possible in tumour tissue samples," says Ulrich Rodeck, M.D., Ph.D., professor of dermatology, cutaneous biology and radiation oncology at Thomas Jefferson University (Jefferson) and co-lead investigator of the study.

Jefferson is a leader in liquid biopsies for cancer.

Massimo Cristofanilli, M.D., director of the Jefferson Breast Care Center at the Sidney Kimmel Cancer Center discovered in 2004 that a blood test could help to predict the prognosis of women with breast cancer. This study established that the number of circulating tumour cells in a blood sample can give doctors a quick and minimally invasive snapshot of whether a patient is likely to respond to treatment or not.

In addition to circulating tumour cells, the blood also contains free-floating cancer DNA, providing researchers with an option to access treatment-relevant gene alterations in blood samples.

The new partnership between Exosome Sciences Inc. and a Jefferson team led by Dr. Rodeck, and Adam Luginbuhl, M.D.,assistant professor of otolaryngology head and neck surgery, will focus on exosomes as a novel liquid biopsy platform.

Exosomes represent a rapidly evolving frontier in liquid biopsy research. They consist of tiny bubbles or sacs pinched off the surface of cells that contain cellular contents such as RNA and proteins enclosed by the cell membrane.

Recently, researchers discovered that cancer cells release large amounts of exosomes. Evidence is building that shedding these exosomes may allow a tumour to become more aggressive, to resist treatment more efficiently and, to suppress the body's attempt to fight the cancer by dampening the cancer-specific immune response.

The team aims to collect blood samples from patients with head and neck cancer, specifically tumors in the oral cavity. Exosome Sciences will separate and characterise tumour-derived exosomes.

Further molecular characterisation of exosomes derived from both, tumour and normal cells will be carried out at Jefferson. The investigators will initially focus on exosome-associated RNA because RNA is abundant in exosomes and can give researchers a sampling of the genes that are currently 'in-use' by a cell.

The inclusion of 'normal' exosome analysis will provide a look at the whole picture of treatment responses encompassing not just diseased but also normal tissues. The goal is to determine whether molecular signatures correlate with and predict patient responses. In future work, exosome protein content will be included in the analysis. It is expected that diverse liquid biopsy techniques will boost the ability to track cancer development and treatment responses in real time providing critical information to adjust treatment approaches.

"Head and neck cancer is an ideal disease entity to study. We'll be able to look at how treatments affect not only tumor behavior, but also the normal tissue based on exosomes profiles, giving us a window into tolerability of treatment," says Dr. Luginbuhl.

Exosome Sciences is a diagnostic subsidiary of Aethlon Medical, a developer of extracorporeal therapies that target the elimination of infectious viruses and tumor-secreted exosomes from the bloodstream.

Liquid biopsies
The ideal cancer treatment is to create a plan that stays one step ahead of the tumour. However, every patient's cancer changes over time and often changes more quickly in response to treatment.

Physicians work to hit this moving target with the best therapies available but there are often several therapies to choose from. That's why it's important for clinicians to determine as quickly as possible when it's time to change therapies from one that either never worked or stopped working to one that will better control your cancer.

However, using standard diagnostics, it can take as long as three months to find out whether the treatment is working or has failed a time span that cancers can exploit, growing and becoming more difficult to treat.

Researchers at Jefferson's Medical Oncology Associates at the Sidney Kimmel Cancer Center have pioneered and implemented new tools to monitor a patient's cancer in real time through a simple blood test.

Since September 2014, Jefferson has been offering patients this new diagnostic blood test, often called a ''liquid biopsy'' or circulating-tumour-cell (CTC) count, to detect cancer cells that have been shed or are actively moving from one site to another into the bloodstream.

The test lets doctors check for changes in the tumor quickly and easily, without repeating additional painful surgical biopsy that aren't a good option for some patients, or scans, which can't detect small increases in growth.

Today, the test is FDA-approved for breast, colon, and prostate cancers that have metastasised, or begun to spread. But Jefferson researchers are working on expanding this to other cancers and have a number of clinical trials open.

Whole body scans, and in some cases tissue biopsies may remain important in tracking the spread and growth of your cancer, but the CTC test provides oncologists with more information more frequently than is possible with other tests and it is particularly important to predict the spreading as a consequence of treatment failure.

All that a doctors need is a small vial of the patient's blood. Solid tumours (in other words, cancers that don't originate in blood cells) will often release individual cancer cells into the bloodstream when the cancer is metastatic, in order to seed the cancer to new locations in the body.

Researchers have discovered that when a blood sample contains a small number of these cells, the tumour is more likely to be stable, with its growth under control the sign of a successful medication. When the number of circulating tumor cells, or CTCs, as they are called is high, the cancer is probably growing and may suggest that it's time for a new course of action.





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