Blood test detects tumor DNA mutations in real time
After being diagnosed, recurrence and/or progression is an normal concern. Imaging has been a typical diagnostic test to detect the cancer returning or progressing. For the last several years, new methods that are Non-invasive are being developed. These Non-invasive cancer tests, known as "Liquid Biopsies" are diagnostic tests that detect circulating tumor DNA (ctDNA) or cell free DNA (cfDNA) in the blood or the urine. Circulating Tumor Cell (CTC) tests are an early version of these Liquid biopsies. These simple tests can reveal breast cancer metastasis, essentially providing live information about disease status. This technology could will likely replace traditional invasive biopsies which are expensive, time consuming, can be painful and risky.
Why is this important?
Imaging technologies (PET, MRI, Mammography, Ultrasound, etc) have not advanced enough to detect progression soon enough. Only when the malignancy has reached a critical point, do they detect it.
Better imaging systems are under development. [Magnetic resonance spectroscopy (MRS) with hyperpolarized 13carbon-enriched substrates (or simply: "Hyperpolarized 13C MRS imaging") is a promising imaging technique that is in early stage clinical trials]
In the meantime, this emerging science of blood / urine tests might have clinical relevance soon.
In Feb 2015, an article was written about Guardant Health's new liquid biopsy, which is used for Stage III & IV cancers. Here's the article: Plasma-Based Biopsies Can Help Guide Therapy: Circulating Tumor DNA
Their product, Guardant360, is a great example of this next generation diagnostic blood test that measures ctDNA.
Here's the concept behind this blood test:
Cancer is genetically unstable and often mutates. There's a strong need to answer when and what those mutations are. Armed with this mutation info, oncologists can implement treatments to deal with the new mutation before progression continues. For example, imagine a cell mutates from HER2- to HER2+. If this simple blood test can discover that mutation in "real time", then introducing the drug Herceptin, an anti-HER2+ treatment would be a wise decision.
As of 2015, the Guardant360 blood test is optimized to detect mutations in Stage III & IV cancers. Eventually Liquid biopsies will have exquisite sensitivity to detect exceedingly low levels of circulating biomarkers, a key underpinning for the development of early minimally invasive cancer screening tools... This is be useful for the early stage patients (Stage 1-2). What remains at this point is clinical validation.
Here is a short list of companies (mostly US based) offering Liquid Biopsy diagnostic tests:
1. Foundation Medicine - Based in Cambridge, Massachusetts. They are a startup backed by Bill Gates and Google Ventures. They seem to be mentioned the most in the media and on this forum. The core product is "FoundationOne". It provides the genomic profile of the tumor. It matches each patient with targeted therapies and clinical trials that are relevant to the molecular changes in their tumor. The test utilizes next-generation sequencing to identify alterations in all genes known to be somatically altered in solid tumors.
2. Personal Genome Diagnostics - Based in Baltimore, Maryland. They have two products: A. "CancerSelect" and _ B. "CancerComplete".
Both tests look at the cancer cells (from a tumor sample) as well as normal tissue (from a saliva / blood sample) to find out what specific genetic changes are present in the cancer cells. They claim to find actionable info in 67% of cases - meaning there is a therapy or clinical trial available that specifically targets the genetic alteration found.
A. CancerSelect is ~$5,850 (partially covered by insurance). It looks at 203 genes and results take 3 weeks.
B. CancerComplete is ~$12,500 (NOT covered by insurance). It looks at 20,000 genes and takes 6 weeks.
3. NantHealth - Based in Southern California. It's a division of NantWorks, which was founded by Dr. Patrick Soon-Shiong, the wealthiest American in the healthcare industry. (He was profiled on the TV show "60 Minutes" in December 2014, which can be watched here and a major force behind the #CancerMoonshot2020 initiative to accelerate progress towards a cure.
4. Caris Life Sciences - Based in Dallas, Texas. Their blood test is called "Carisome Technology". It identifies and characterizes cMVs (sub-cellular membrane-bound vesicles) in the blood, thereby creating disease-specific biosignatures, which can be made up of a combination of biomarkers. The unique cMV biosignature can then be used to drive diagnosis, prognosis and the measurement of therapeutic response (predictive). Despite being in the US, the .eu in their website address leads me to believe this service is targeted for Europe.
5. Illumina - Based in San Diego, California. They are one of the leaders in Full Genome sequencing and array-based diagnostic tools. illumina is working on building and clinically validating a library of circulating tumor DNA (the genetic fragments that can be detected with a blood test). They are in the research phase of building that library: Sampling solid tumors and matched blood specimens and sequencing both the cellular DNA and the blood fragment DNA.
6. GRAIL - Based in San Francisco, California. In Jan 2016, Illumina created a new company called GRAIL Bio. Powered by Illumina sequencing technology, GRAIL will develop a pan-cancer screening test by directly measuring circulating nucleic acids in blood. They are building on "ultra-deep sequencing" technology and big data/machine learning to create a highly-accurate pan-cancer blood test.
x-Google executive Jeff Huber, lost his wife to cancer in Nov 2015 and joined Grail as their CEO in Feb 2016.
7. Trovagene - Based in San Diego, California
This early stage start-up is focused on blood based circulating tumor DNA (ctDNA) and urine based ctDNA tests.
8. Biocept, Inc - Based in San Diego, California
Biocept (Nasdaq: BIOC) specializes in circulating tumor cell (CTC) and biomarker analysis from liquid biopsies to improve the diagnosis and treatment of women with recurrent or newly diagnosed MBC. CTCs can be detected, although at a lower frequency, in early stage cancers. They can also analyze the CTC's for ER expression and HER2.
9. Genomic Health - Based in Redwood City, California
Makers of Oncotype DX, the genomic test that analyzes specific genes used to predict how a cancer might behave, Genomic Health released this news describing their plans to introduce its first liquid biopsy-based test in 2016.
10. Angle plc - Based in Guildford, Surrey, UK
Lead product is the Parsortix cell separation system, which can capture very rare cells from blood. This includes circulating tumor cells (CTCs) in cancer patient blood - even when there is less than one CTC in one billion healthy cells. The resulting liquid biopsy (simple blood test) enables the investigation of mutations in the patient's cancer.
11. Miroculus - Based in San Francisco, California
They created an accurate, easy to use, non-invasive and affordable microRNA detection platform to diagnose, treat and monitor cancer at an early stage. They do this through the examination of microRNAs. microRNAs are small molecules that regulate gene expression. Evidence is mounting that they may be good Biomarkers to detect early stages of cancer.
Here's an April 2015 media article for Miroculus and their pursuit of clinical validation. Gastric cancer is their initial focus.
12. Vortex Biosciences - Based in Menlo Park, California
Based on technology created at UCLA, Vortex is developing a novel liquid biopsy technology, cost effective and high speed, for the isolation and detection of these CTCs from human blood.
13. Pathway Genomics - Based in San Diego, California
They released their CancerIntercept liquid biopsy in early September 2015, although the FDA is investigating the validity of their product claims, which can be read here.
14. Qiagen - Based in Germany. In 2015, it acquired AdnaGen's (also based in Germany) circulating tumor cell enrichment technology to improve its capabilities in liquid biopsies.
15. RainDance Technologies - Boston, Massachusetts
16. Boreal Genomics - Mountain View, California
17. Adaptive Biotechnologies - Seattle, Washington
18. Sysmex Inostics - Chicago, illinois
19. Exosomedx - Boston, Massachusetts
20. Top medical schools have also developed their own Liquid Biopsy and use them as research tools. Examples include:
- Massachusetts General Hospital liquid biopsy examines tumor RNA picked up in circulating platelets (platelet RNA). Source: Nov 2015.
Comments
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This is news from Aug 2014, but useful for the curious who have interest in the next generation of blood diagnostics.
A Floating Autoboigraphy of a Cancer
There's a new way of monitoring and studying cancer, by tracking fragments of DNA that are released by tumors and travel around in the blood. This "circulating tumor DNA" can give away the presence and progress of a tumor. It also allows clinicians to study a cancer patient's mutations, and potentially better tailor their treatments, without having to perform invasive (and often uninformative) biopsies.
When cancer cells rupture and die, they release their contents, including circulating tumour DNA (ctDNA): genome fragments that float freely through the bloodstream. Debris from normal cells is normally mopped up and destroyed by 'cleaning cells' such as macrophages, but tumours are so large and their cells multiply so quickly that the cleaners cannot cope completely.
By developing and refining techniques for measuring and sequencing tumour DNA in the bloodstream, scientists are turning vials of blood into 'liquid biopsies' - portraits of a cancer that are much more comprehensive than the keyhole peeps that conventional biopsies provide. Taken over time, such blood samples would show clinicians whether treatments are working and whether tumours are evolving resistance.
As ever, there are caveats. Levels of ctDNA vary a lot from person to person and can be hard to detect, especially for small tumours in their early stages. And most studies so far have dealt with only handfuls or dozens of patients, with just a few types of cancer. Although the results are promising, they must be validated in larger studies before it will be clear whether ctDNA truly offers an accurate view - and, more importantly, whether it can save or improve lives. "Just monitoring your tumour isn't good enough," says Luis Diaz, an oncologist at Johns Hopkins University in Baltimore, Maryland. "The challenge that we face is finding true utility."
If researchers can clear those hurdles, liquid biopsies could help clinicians to make better choices for treatment and to adjust those decisions as conditions change, says Victor Velculescu, a genetic oncologist at Johns Hopkins. Moreover, the work might provide new therapeutic targets. "It will help bring personalized medicine to reality," says Velculescu. "It's a game-changer."
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http://www.sciencedaily.com/releases/2015/04/15041...
New blood test can predict future breast cancer
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http://www.sciencedaily.com/releases/2015/04/15041...
Potential for prediction of progression for early form of breast cancer
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This is amazing news. I just saw an article, I think on the same study, and wanted to make sure that everyone was aware of it. IMO, another game changer for future generations. http://www.sciencealert.com/new-blood-test-can-predict-breast-cancer-five-years-before-it-develops
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The 800 lb gorilla, illumina (Full-genome sequencing & array-based diagnostic tools) has entered the liquid biopsy industry. Here's a media article from yesterday called: "The Future of Cancer Treatment is (Almost) Here".
Tina Nova, VP of Oncology, describes how they're building and clinically validating a library of circulating tumor DNA (the genetic fragments that can be detected with a blood test). -
Here's another article released today which explains how a liquid biopsy can detect recurrence months before it normally would have been found.
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I appreciate you guys posting the research, but I guess I'm missing why this is awesome. So you find out a little sooner that you have metastatic disease.....then what? Unless something has changed of which I am not aware, whether you have a little or a lot, the prognosis and treatment are the same and either treatment will work or it won't. This kind of advancement doesn't really blow my hair back. Actually , it kind of makes me sad that those research dollars weren't spent on better (and more humane) treatments. Poisoning is getting kind of old.
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Leggo,
I was thinking the same thing....if they can't do something about the fact they know, why know. Sort of like alzheimer's disease right now. Hopefully by knowing sooner, someone smart will figure out a way to turn the cells off or kill them with new genetic information.
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I think this is exciting because it may be the first step toward liquid biopsies in lieu of onerous and expensive high risk screening - before ANY cancer can be detected with current methods.
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I get what you're saying Lucy. I guess I just can't get excited about finding ANY cancer in a more efficient, less costly way. Doesn't really change anything whether it's a new diagnosis or a metastatic one. I can see how most would feel differently though. Wish my first reaction wasn't "so what?" because I really should be grateful for something new. Less scanning, more money for treatment I guess? I suppose I could rationalize it that way, but it still makes me sad because TREATMENT advances suck. Should make for some educational discussion, so thanks for posting the links guys.
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This article is from last year.
In June, she had a test of tumor DNA fragments in her blood developed by a start-up called Guardant Health. It found a genetic mutation that suggested her disease would be susceptible to the drug Afinitor.
Ms. Lewis, however, had previously tried Afinitor and it had stopped working. Nonetheless, she tried it again. And again, it didn’t work. A second test in December found several more mutations but did not lead to a clear choice of treatments.
But a different liquid biopsy found that at least some of Ms. Lewis’s cancer cells had abundant amounts of the protein Her2, which drives tumor growth. That had not been seen on her tissue biopsies, perhaps because such biopsies sample only a tiny bit of what is typically a heterogeneous tumor.
As a result, Ms. Lewis has just started on Herceptin and Tykerb, two drugs for Her2-positive cancers.
I have tried the regular liquid biopsies which look for tumor cells (found a lot one year and none a year later, both while NED on scans).
They tried another approach a year ago (stiill NED on scans) to see about changed HER2 status and the possibility of taking Herceptin. They did not find anything so I am still on the same treatment.
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http://medicalxpress.com/news/2015-05-blood-liquid...
New blood tests, liquid biopsies, may transform cancer care
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While visiting, last year, the Rare Breast Cancer Research Lab at Sloan Kettering, the researchers explained to me how they were able to identify progression, using blood markers, of metastatic disease before imaging identified it AND before patients became symptomatic. This breathtaking discovery meant that treatments could be changed more quickly. They refer to blood markers as "liquid gold."
Furthermore, as Dr. Eric Topol mentions in his prior book, The Creative Destruction of Medicine, researchers and physicians alike, will one day soon, demonstrate that population based screening will no longer be necessary. Blood tests markers will determine who is at higher risk at getting a disease or a recurrence of a disease and will be screened accordingly.
In his latest book, The Patient Will See You now, Dr. Topol goes further by describing, the "quest to provide individualized medicine, knowing the biology of a person via genomics (and all the "omics" including proteomics, metabolomics, epigenomics, and "biomarkers") is one essential step. The other goal is knowing about the individual's physiology. This has become possible through the use of non-invasive wireless sensors that can continuously collect data on such metrics as blood pressure, heart rhythm and rate, oxygen saturation in the blood, blood glucose, and many more."
These radical discoveries should change how clinical trials are conducted AND also lead to better screening and treatment making decisions.
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Thanks voracious. I requested Dr. Topol's book from my local library and will pick it soon.
Here's another media article written yesterday about Liquid Biopsies. This one paints a negative picture though. It essentially says we have a long way to go, which I don't disagree with.
"The Great Cancer Test Experiment" -
Hi Heidihill, you say you have tried so-called liquid biopsies with inconsistent results. Would you mind sharing your oncologist's take on the results and explanation if any?
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The first time I was shocked that there were so many tumor cells (not DNA fragments), and my onc reassured me that was not much, like smaller than a pinhead if you put it all together. They were still ER/PR+. With the 0 results, I didn't ask for an explanation.
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Thank you, Heidihill
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This is one more example of how non-invasive Liquid biopsies are the future.
"Blood test detects when hormone treatment for breast cancer stops working"
Today, UK based researchers announced that they developed a highly sensitive blood test that can spot when breast cancers become resistant to AI hormone therapy. The test detected mutations in the ESR1 gene, which has been known to be one mechanism of resistance.
This is very relevant for the hormone receptor-positive (HR+) cohort. This research applied to Aromatase Inhibitor's (AI's) only.ESR1 mutations are rare in newly diagnosed, untreated breast cancers, but appear to be frequently acquired during progression to hormone resistance, especially in the context of estrogen deprivation therapy (AI's, Tamoxifen, etc).
This liquid biopsy will allow oncologists to change to a different therapy if patients develop this mutation.
Regardless if ILC or IDC, this is a big deal and great news for the Hormone Receptor (HR+) cohort taking AI's.
The research applies to AIs only, not Tamoxifen. -
Here's another example of the potential power of liquid biopsies.
National Institutes of Health researchers have identified a striking signature in tumor DNA that occurs in five different types of cancer (colon, lung, breast, stomach, and endometrial).
Now deemed as a possible universal cancer biomarker, the gene ZNF154, had a elevated methylation signature. This is an epigenetic mechanism.
It could lead to a blood test to identify early cancers.Media version: NIH researchers identify striking genomic signature shared by five types of cancer
Science version: Robust Detection of DNA Hypermethylation of ZNF154 as a Pan-Cancer Locus with in Silico Modeling for Blood-Based Diagnostic Development
Epigenetic modifications can be targeted with HDAC inhibitors, so this might be relevant for existing patients.
I'll email the researcher to find out. -
Thanks so much for your research.
Here's what I find really surprising. "Tumor DNA in a person with cancer typically comprises between 1 and 10 percent of all DNA circulating in the blood stream." That seems to be a huge amount.
This is really exciting, game changing stuff.
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