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Exosomes to the rescue?
WALTHAM, Mass.—With more than 250,000 cases diagnosed per year, breast cancer is the most pervasive cancer in women. While early detection is critical, currently available liquid biopsy approaches may not be able to detect rare markers of the disease.
However, exosomes reflect active cellular processes to enable early cancer detection and, in April, Exosome Diagnostics presented evidence that breast cancer exosomes isolated from plasma of stage 1 and stage 2 breast cancer patients provide the same RNA signature as matched tumor tissue.
At the American Association for Cancer Research’s AACR 2018 meeting in Chicago recently, Dr. Sudipto Chakrabortty explained how liquid biopsies can obtain tumor-specific information from biofluids such as blood or plasma. Because every tumor has unique molecular changes, the ability to monitor these changes with a blood sample, instead of an invasive tissue biopsy, provides a way to give patients access to the best treatment option. An exosomal liquid biopsy enables clinicians to determine the unique RNA profiles of breast cancer tissue in blood, without using tissue samples.
Exosomes are small vesicles actively secreted from tumor cells as well as normal cells. They contain all of the information from the cell that released them, including RNA and proteins. Biofluids, including blood and plasma, are very complex and encompass material from both the tumor and from the normal processes in the body.
Presented as an AACR poster session called “Exosomal liquid biopsy reveals mRNA and lincRNA biomarkers in early stage breast cancer patient plasma,” the study used a breast cancer-specific marker to isolate breast cancer-specific exosomes from blood. It then analyzed the total RNA content from the samples by using RNAseq. Chakrabortty and his team also sequenced RNA from matched formalin-fixed paraffin-embedded (FFPE) tissue samples from these patients.
Johan Skog, chief scientific officer at Exosome Diagnostics, said he was astonished by the result, noting: “Not only could we accurately identify breast cancer RNA signatures from the plasma samples, but we could even see that the breast cancer exosomes from a patient clustered perfectly next to its matched FFPE tissue sample. This is remarkable, considering that every patient is unique.”
Skog added, “We have previously shown that we can increase performance of mutation testing compared to cell-free DNA assays by combining exosome RNA and cell-free DNA, but this study with cancer-specific exosome enrichment changes the game completely. This capability (Exosome’s patented ExoDx Depletion/Enrichment [EDDE] technology) allows us to see the actual RNA signatures from the tissue from as little as 1 ml of plasma, obviating the need for tissue to analyze tumor specific RNA changes.
“We saw the same breadth and diversity of RNA as we saw from the tissue samples, with more than 12,000 different mRNAs and over 1,000 lincRNAs. The breast cancer-specific exosomes looked almost identical to the matched tissue. This was not seen when sequencing plasma exosomes without the enrichment. This leap forward has not been easy and builds on years of research at Exosome Diagnostics on how to best enrich tissue-specific exosomes from biofluids, methods that are built into the proprietary EDDE platform.”
The EDDE platform is designed to remove non-relevant exosomes from plasma, according to Skog. Using this platform, the company identified a plasma exosomal RNA signature associated with durable response to immunotherapy in cancer patients. Exosomes reflect active cellular processes, enabling early cancer detection. Exosome-based liquid biopsy is minimally invasive and highly sensitive, using techniques to enhance signal-to-noise. It enriches specific exosomal subpopulations originating from a tumor or any tissue of interest and depletes non-relevant, non-cancerous exosomes originating from abundant cell-types such as blood cells.
Skog, a pioneer in the field of exosomal research, has built methodologies to analyze disease specific RNA, DNA and proteins from biofluids. By using these patented methodologies and proprietary analysis pipelines, Exosome can achieve sensitive results, with very low sample volumes.
According to Exosome President and CEO John Boyce, “This first-of-its-kind data proves that Exosome Diagnostics’ liquid biopsy is the solution to obviate tissue biopsies and improve patient care.”