Five Reasons to Get More Magnesium

If you feel tired, weak, or nauseated… You might have a magnesium deficiency. And you’re definitely not alone. In fact, most people don’t have enough.1

 INH ResearchJanuary 9, 2015

And talk about dangerous… This powerful mineral keeps us healthy and prevents serious ailments. Things like hypertension and osteoporosis. But there’s even more to it than that.

Here are five reasons to get more magnesium.

1. Stops Anxiety: Magnesium supports your nervous system. Low levels cause a disruption. This can lead to anxiety and depression. Some experts even believe a magnesium deficiency is a direct cause of depression…2 And about half of the people diagnosed with depression also have anxiety.

Most doctors throw dangerous drugs—like benzodiazepines—at people with anxiety or depression. But just three months of use can raise your Alzheimer’s risk by 51% (among other dangers). Yet numerous studies show that magnesium eased depression and anxiety where these drugs failed. Without any side effects.3

2. Eases Stress: It doesn’t just support your nervous system. Magnesium stops cortisol levels from getting too high. It also helps your body produce melatonin which makes it easier to relax and fall asleep.4 Magnesium may help you fight headaches and fatigue. These are two of the most common signs of stress.

When you’re under stress, your body uses up magnesium faster.5 The result? Even more stress. It can also steal this mineral away from your bones and heart. This is why getting more magnesium from your diet alone may not be enough.

3. Prevents Diabetes: Magnesium can help keep your glucose levels under control. Just look at pistachios. They’re rich in magnesium. One study revealed eating 100 pistachios a day helped lower blood sugar levels by 78%.6

Another study found high magnesium intake cuts risks of diabetes by 33%.7 It can also reduce insulin sensitivity. Diabetics who took 365 mg a day significantly lowered insulin resistance after six months.8

4. Fights Cancer: Magnesium helps lower your colorectal cancer risk. About 95% of cases are adenocarcinomas. They begin with a tumor growth. Eventually, these growths can turn cancerous. Yet every 100 mg of magnesium you add to your diet each day lowers your risk of a growth ever developing by 13%. And if you already have a growth, you can reduce the odds of it becoming cancerous by 12%.

Magnesium may also help you avoid pancreatic cancer. One study found just two handfuls of magnesium-rich nuts a week can reduce your risk by 35%.

5. Keeps Telomeres Long: It’s the key to looking younger and living longer… Telomerase is the enzyme that controls the length of your telomeres. Without enough, you may age even faster. And this enzyme depends on magnesium. The mineral helps replicate and stabilize DNA.9

This might be the reason why people die of a magnesium deficiency… Researchers found low levels of magnesium increases death risk by 85%.10 Not getting enough of this mineral could kill you in as little as 10 years.

A magnesium-rich diet contains about 400 mg a day. This might sound like a lot. But it’s not as hard as it seems. Salads are a great start. Try spinach, chopped almonds, avocados, and shrimp. One square of organic dark chocolate contains 95 mg of magnesium.11

You can also find a magnesium supplement. Just make sure you read the label before purchasing. Look for one that gives you at least 200 mg per serving of natural magnesium.

References:
1http://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/
2http://george-eby-research.com/html/magnesium-for-depression.pdf
3http://www.psychologytoday.com/blog/evolutionary-psychiatry/201106/magnesium-and-the-brain-the-original-chill-pill
4http://www.mensjournal.com/health-fitness/health/magnesium-the-missing-mineral-20140117
5http://www.calmclinic.com/anxiety/drugs/magnesium
6http://care.diabetesjournals.org/content/early/2014/08/07/dc14-1431.abstract
7http://www.ncbi.nlm.nih.gov/pubmed/14693979%20
8http://www.diabetesincontrol.com/articles/diabetes-news/15873-type-2-diabetes-risk-lowered-with-magnesium-intake
9http://www.ncbi.nlm.nih.gov/pubmed/22379366
10http://www.ncbi.nlm.nih.gov/pubmed/21703623
11http://www.healthaliciousness.com/articles/foods-high-in-magnesium.php

https://www.institutefornaturalhealing.com/2015/01/five-reasons-to-get-more-magnesium/

CRISPR Gene Editing Fixes Muscular Dystrophy in Dogs. Are Humans Next?

The powerful gene editing technology CRISPR is one small step closer to treating a human disease.

By ALICE PARK 

August 30, 2018

In a new paper published in Science, researchers led by Eric Olson, professor and chair of molecular biology at UT Southwestern Medical Center, reported that he and his team successfully used CRISPR to correct the genetic defect responsible for Duchenne muscular dystrophy in four beagles bred with the disease-causing gene. It’s the first use of CRISPR to treat muscular dystrophy in a large animal. (Previous studies had tested the technology on rodents.) In varying degrees, the genetic therapy halted the muscle degradation associated with the disease.

Duchenne is caused by mutations in the dystrophin gene, which codes for a protein essential for normal muscle function. People born with the disease are often eventually confined to wheelchairs as their muscles continue to weaken, and in the later stages, many rely on ventilators to breathe as their diaphragm muscles stop working. Eventually, they develop heart and respiratory failure.

Olson and his team “fixed” the mutated dystrophin gene in four dogs by splicing out an offending section of the gene using CRISPR. The gene editing technology, discovered in 2012, can cut out sections of DNA at precise locations (and also potentially introduce new DNA as well). In the case of Duchenne, says Olson, simply snipping out a section of the mutated dystrophin gene allows the gene to make enough of the proper protein that muscles need to function.

Olson tried two different methods of injecting the CRISPR molecular scissors. With two dogs he directly injected the CRISPR technology into muscle, while in two other dogs he injected the same CRISPR technology into the bloodstream, so it could travel to more parts of the body and have a broader effect on different types of muscle from the limbs to the heart and diaphragm. Because Duchenne seems to affect the heart and respiratory system muscle preferentially, he also loaded the CRISPR cutting complex onto a molecular vehicle, a cold virus that was modified to seek out and splice DNA in those muscle cells in particular.

“I was frankly exuberant by the results,” says Olson. “It was jaw dropping.”

In the dogs that had received the systemic injections, he found that muscle cells in various parts of their bodies, including the heart and diaphragm, were churning out healthy dystrophin protein at anywhere from 3% to 90% of the normal levels eight weeks after injection. Olson says that muscular dystrophy experts believe that if dystrophin levels in affected people were raised to 15% of normal, it would make a dramatic difference in their lives and their ability to function. The dogs receiving the CRISPR injections directly into their muscle also showed higher levels of dystrophin production, but just in those muscles specifically. Because Duchenne affects deep organs like the heart and respiratory system, Olson says finding a way to deliver CRISPR more widely, without repeated and multiple injections, is preferable.

The idea is that CRISPR would essentially delete the mutation in muscle cells, and return the affected dogs to a nearly normal state. So far, the animals continue to make higher amounts of dystrophin after eight weeks.

The study is the latest in an encouraging string of results in applying CRISPR to treat human disease. Researchers have also successfully used the gene editing technology to splice out HIV from both infected human cells in the laband in living mice and rats, and are close to beginning trials to blood disorders like beta thalassemia and sickle cell anemia. Scientists have even corrected a genetic heart defect in embryos in the lab, which were not allowed to develop further or be implanted for ethical reasons. While serious questions about the safety of CRISPR-based therapies remain — some studies revealed greater than expected side effects from overzealous DNA snipping, for example — both academic and commercial researchers remain committed to investigating CRISPR as a new tool in addressing genetic diseases such as Duchenne.

Olson is encouraged by the results, even if they came from just a few dogs. They provide some reassurance that Duchenne, which is often diagnosed before people start to notice symptoms of muscle weakness, might be halted in its tracks before important skeletal, heart and breathing muscle are damaged beyond saving. A CRISPR-based therapy, he says, may be most effective in treating young people recently diagnosed with the disease, to prevent them from ever experiencing the symptoms of Duchenne.

Even people with more advanced disease might benefit, Olson thinks, as long as there is some muscle left to maintain a certain level of function, whether that’s moving the legs and arms or keeping the heart functioning. “I absolutely believe that whatever stage we intervene with this therapy, it could halt or slow the progression of the disease from that point forward,” he says.

First, however, more studies need to be done in larger animals like dogs. Olson is planning on a longer term study to see how long the CRISPR cells remain in the dogs, and how safe the therapy is.

The hope is that if those animal studies and human trials prove this technique is safe and effective, CRISPR could potentially lead to a cure for Duchenne, Olson says. “We are going for a cure, not a treatment,” he says. “All of the other therapies so far for Duchenne muscular dystrophy have treated the symptoms and consequences of the disease. This is going right at the root cause of the genetic mutation.”

http://time.com/5382101/crispr-muscular-dystrophy-in-dogs/

'Exciting' blood test spots cancer a year early

Doctors have spotted cancer coming back up to a year before normal scans in an "exciting" discovery.

The UK team was able to scour the blood for signs of cancer while it was just a tiny cluster of cells invisible to X-ray or CT scans.

By James Gallagher Health and science reporter, BBC News website

• 26 April 2017

• 

Doctors have spotted cancer coming back up to a year before normal scans in an "exciting" discovery.

The UK team was able to scour the blood for signs of cancer while it was just a tiny cluster of cells invisible to X-ray or CT scans.

It should allow doctors to hit the tumour earlier and increase the chances of a cure.

They also have new ideas for drugs after finding how unstable DNA fuels rampant cancer development.

The research project was on lung cancer, but the processes studied are so fundamental that they should apply across all cancer types.

Lung cancer kills more people than any other type of tumour and the point of the study is to track how it can "evolve" into a killer that spreads through the body.

Blood test

In order to test for cancer coming back, doctors need to know what to look for.

In the trial, funded by Cancer Research UK, samples were taken from the lung tumour when it was removed during surgery.

A team at the Francis Crick Institute, in London, then analysed the tumour's defective DNA to build up a genetic fingerprint of each patient's cancer.

Then blood tests were taken every three months after the surgery to see if tiny traces of cancer DNA re-emerged.

The results, outlined in the journal Nature, showed cancer recurrence could be detected up to a year before any other method available to medicine.

The tumours are thought to have a volume of just 0.3 cubic millimetres when the blood test catches them.

'New hope'

Dr Christopher Abbosh, from the UCL Cancer Institute, said: "We can identify patients to treat even if they have no clinical signs of disease, and also monitor how well therapies are working.

"This represents new hope for combating lung cancer relapse following surgery, which occurs in up to half of all patients."

So far, it has been an early warning system for 13 out of 14 patients whose illness recurred, as well as giving others an all-clear.

In theory, it should be easier to kill the cancer while it is still tiny rather than after it has grown and become visible again.

However, this needs testing.

Prof Charles Swanton, from the Francis Crick Institute, told the BBC: "We can now set up clinical trials to ask the fundamental question - if you treat people's disease when there's no evidence of cancer on a CT scan or a chest X-ray can we increase the cure rate?

"We hope that by treating the disease when there are very few cells in the body that we'll be able to increase the chance of curing a patient."

---

Janet Maitland, 65, from London, is one of the patients taking part in the trial.

She has watched lung cancer take the life of her husband and was diagnosed herself last year.

She told the BBC: "It was my worst nightmare getting lung cancer, and it was like my worse nightmare came true, so I was devastated and terrified."

But she had the cancer removed and now doctors say she has a 75% chance of being cancer-free in five years.

"It's like going from terror to joy, from thinking that I was never going to get better to feeling like a miracle's been acted," she said.

And taking part in a trial that should improve the chances for patients in the future is a huge comfort for her.

"I feel very privileged," she added.

---

Evolution

The blood test is actually the second breakthrough in the massive project to deepen understanding of lung cancer.

A bigger analysis, published in the New England Journal of Medicine, showed the key factor - genetic instability - that predicted whether the cancer would return.

Multiple samples from 100 patients containing 4.5 trillion base pairs of DNA were analysed.

DNA is packaged up into sets of chromosomes containing thousands of genetic instructions.

The team at the Francis Crick Institute showed tumours with more "chromosomal chaos" - the ability to readily reshuffle large amounts of their DNA to alter thousands of genetic instructions - were those most likely to come back.

Prof Charles Swanton, one of the researchers, told the BBC News website: "You've got a system in place where a cancer cell can alter its behaviour very rapidly by gaining or losing whole chromosomes or parts of chromosomes.

"It is evolution on steroids."

That allows the tumour to develop resistance to drugs, the ability to hide from the immune system or the skills to move to other tissues in the body.

'Exciting'

The first implication of the research is for drug development - by understanding the key role of chromosomal instability, scientists can find ways to stop it.

Prof Swanton told me: "I hope we'll be able to generate new approaches to limit it and bring evolution back from the brink, perhaps reduce the evolutionary capacity of tumours and hopefully stop them adapting.

"It's exciting on multiple levels."

The scientists say they are only scratching the surface of what can be achieved by analysing the DNA of cancers.

http://www.bbc.co.uk/news/health-39658680

Chief medical officer calls for gene testing revolution

Cancer patients should be routinely offered DNA tests to help select the best treatments for them, according to England's chief medical officer. 

By Michelle Roberts Health editor, BBC News online

• 2 hours ago

Cancer patients should be routinely offered DNA tests to help select the best treatments for them, according to England's chief medical officer. 

Prof Dame Sally Davies says in her annual report that the NHS must deliver her "genomic dream" within five years.

Over 31,000 NHS patients, including some with cancer, have already had their entire genetic code sequenced.

Dame Sally wants whole genome screening (WGS) to become as standard as blood tests and biopsies.

Personalised medicine

Humans have about 20,000 genes - bits of DNA code or instructions that control how our bodies works.

Tiny errors in this code can lead to cancer and other illnesses.
Sometimes these mistakes are inherited from a parent, but most of the time they happen in previously healthy cells.

WGS - which costs about £700 - can reveal these errors by comparing tumour and normal DNA samples from the patient.

Dame Sally says that in about two-thirds of cases, this information can then improve their diagnosis and care.

Doctors can tailor treatments to the individual, picking the drugs mostly likely to be effective.

And WGS can also show which patients are unlikely to benefit, so they can avoid having unnecessary drugs and unpleasant side-effects.

Quicker diagnosis

Dame Sally wants DNA testing to become standard across cancer care, as well as some other areas of medicine, including rare diseases and infections.

"I want the NHS across the whole breadth to be offering genomic medicine - that means diagnosis of our genes - to patients where they can possibly benefit," her report says.

People with rare diseases could benefit from having greater access to the technology, speeding up diagnosis.

Doctors are already using genetic tests to identify and better treat different strains of the infectious disease tuberculosis.

Dame Sally said patients could be assured that their genetic data would be stored securely and "de-identified" so that their privacy would be protected.

---

The Genomic Dream

Image copyright D3Damon/Getty

Over 10 years ago, international scientists reached a breakthrough in DNA work - sequencing the entire genetic blueprint of man. The Human Genome Project meant experts now had a catalogue of DNA code to explore and refer to.

They began to understand which genes controlled which processes in the body and how these could go wrong.

Doctors then started to "read" a patient's DNA to get a better idea of what might be causing their symptoms and how best to treat their illness.

Genomic medicine - tailoring care based on an individual's unique genetic code - is now transforming the way people are cared for by the NHS.

Genes can predict if a woman with breast cancer might respond to certain drugs, or whether radiotherapy is likely to shrink a tumour, for example.

---

Currently, genetic testing of NHS patients in England is done at 25 regional laboratories, as well as some other small centres.

Dame Sally wants to centralise the service and set up a national network to ensure equal access to the testing across the country.

A new National Genomics Board would be set up, chaired by a minister, to oversee the expansion and development of genomic services.

Sensitive data

Dame Sally told BBC Breakfast that a lot of money was being spent because it was currently operating like a "cottage industry".

By having centralised laboratories, more could be done with the money, including keeping up with the latest technology, she said.

She said one hurdle could be doctors themselves, who "don't like change", and she urged cancer service patients to press their doctors to move from a local to a national service.

She also said patients must understand they needed to allow use of their data, alongside other data, in order to get the best diagnosis, and therefore the best treatment.

Phil Booth, from campaigning organisation, MedConfidential, said this move had "huge potential" for patients and the NHS, but there were "great risks with large collections of sensitive data".

"Every single use of patient data must be consensual, safe and transparent," he told BBC Radio Four's Today programme, and patients should be able to opt-out if they so wish.

http://www.bbc.co.uk/news/health-40479533

New blood test for advanced prostate cancer

A revolutionary three-in-one blood test could pave the way to precision-personalised treatment for advanced prostate cancer, say scientists.

By PA  19 Jun 2017, 0:15

Updated: 19 Jun 2017, 0:15

The test has the potential to transform the way the disease is tackled by targeting specific gene mutations, it is claimed.

By looking for cancer DNA in blood samples, researchers were able to identify men with defective BRCA genes who were likely to benefit from a class of drugs called PARP inhibitors.

They also used the test to monitor DNA in the blood after treatment started, so patients who were not responding could quickly be switched to an alternative therapy.

Finally, the same test was used to pick up signs of evolving cancer showing the first signs of drug resistance.

Professor Johann de Bono, who led the team at The Institute of Cancer Research in London, said: "We were able to develop a powerful, three-in-one test that could in future be used to help doctors select treatment, check whether it is working and monitor the cancer in the longer term.

"We think it could be used to make clinical decisions about whether a PARP inhibitor is working within as little as four to eight weeks of starting therapy.

"Not only could the test have a major impact on treatment of prostate cancer, but it could also be adapted to open up the possibility of precision medicine to patients with other types of cancer as well."

In future, the test could allow the PARP inhibitor olaparib to become a standard treatment for advanced prostate cancer, by targeting those most likely to benefit, picking up early signs that the drug might not be working, and monitoring for emerging resistance.

PARP inhibitors such as olaparib block an enzyme used by cancer cells with defective BRCA 1 and 2 genes to repair their DNA.

When PARP is disabled, the cells die. 

The drugs do not generally work on cancer cells with functioning BRCA genes, because these are primary DNA repair tools that make PARP unnecessary.

While some patients respond to the drugs for years, others either fail to respond at an early stage or develop resistant cancer.

The new test, described in the journal Cancer Discovery, was developed with the help of 49 patients enrolled in TOPARP-A, a Phase II clinical trial investigating the effectiveness of olaparib.

Men responding to the drug were found to experience an average drop in circulating cancer DNA of 49.6% after eight weeks of treatment. In contrast, cancer DNA levels rose by 2.1% in patients who did not respond.

Patients whose cancer DNA blood levels were lowered by olaparib survived an average of 17 months compared with 10.1 months for those whose levels remained high.

The scientists also conducted a detailed investigation of the genetic changes in cancer DNA among men who stopped responding to olaparib.

They found that the cells acquired genetic changes that cancelled out the DNA repair defects making them susceptible to the drug.

Professor Paul Workman, chief executive of the Institute of Cancer Research, said: "Blood tests for cancer promise to be truly revolutionary.

"They are cheap and simple to use, but most importantly, because they aren't invasive, they can be employed or applied to routinely monitor patients to spot early if treatment is failing - offering patients the best chance of surviving their disease.

"This test is particularly exciting because it is multi-purpose, designed for use both before and after treatment, and using both the absolute amounts of cancer DNA in the bloodstream and also a readout of the specific mutations within that genetic material.

"We believe it can usher in a new era of precision medicine for prostate cancer."

Each year, around 47,000 men in the UK are diagnosed with prostate cancer and more than 11,000 die from the disease.

Dr Matthew Hobbs, deputy director of research at the charity Prostate Cancer UK, which funded the research, said: "It's clear that we need to move away from the current one-size-fits-all approach to much more targeted treatment methods.

"The results from this study and others like it are crucial as they give an important understanding of the factors that drive certain prostate cancers, or make them vulnerable to specific treatments."

http://www.aol.co.uk/living/2017/06/18/new-blood-test-could-see-personalised-treatment-for-advanced-pr/

Tumor DNA in Bloodstream May Yield New Cancer Insights

For many people with cancer, the needle biopsy — an invasive procedure that isolates tumor tissue for analysis — is an uncomfortable part of diagnosis and treatment. Recent research reveals that the information obtained from this biopsy might be less accurate than previously thought.

By Jim Stallard 

on Monday, August 11, 2014

Experimental pathologist Jorge Reis-Filho says “liquid biopsies” could provide more comprehensive ways to assess tumors.

Summary

Experimental pathologist Jorge Reis-Filho explains how tumor DNA obtained from the blood could lead to noninvasive — yet highly sensitive — ways of detecting and monitoring cancer in the body.

For many people with cancer, the needle biopsy — an invasive procedure that isolates tumor tissue for analysis — is an uncomfortable part of diagnosis and treatment. Recent research reveals that the information obtained from this biopsy might be less accurate than previously thought.

As researchers identify genetic changes that trigger cancer and promote its growth, there is a growing awareness that effective treatments could be undermined by tumor heterogeneity — the variation among cancer cells both within the primary tumor and within distinct tumors formed by a cancer’s spread, or metastasis, to distant sites. For example, genetic mutations present in one biopsy sample might be absent from another biopsy taken from a different part of the tumor. This type of discrepancy complicates clinical decisions and confounds research efforts.

Now scientists are looking for less invasive and more comprehensive ways to examine tumors. One approach might be to rely on “liquid biopsies,” which analyze tumor cells or tumor cell DNA that has entered the bloodstream simply by drawing a blood sample from the patient.

Memorial Sloan Kettering experimental pathologist Jorge Reis-Filho, who studies the genetic alterations that drive the malignant behavior of breast cancer cells, discussed with us the potential of analyzing circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs) in a blood sample and explained ways that ctDNA might provide insights for treatments that go beyond current conventional clinical tests.

What are the differences between CTCs and ctDNA and what can they reveal about a tumor?

CTCs have been recognized over the last decade as clinically useful cancer biomarkers in certain cases, but researchers have recently begun to focus on ctDNA as a potentially superior source of genetic information.

One limitation of CTCs is that they require elaborate methods for detection and retrieval. First, they need to be isolated from other blood material, which is difficult because they are very rare. Then extracting the DNA to study the genetic makeup of the cells is itself a cumbersome process. In addition, it is unclear what causes cells to break off from a tumor. We don’t know whether CTCs represent the entire makeup of cancer cells in the tumor or only a subpopulation, so it has yet to be defined how many CTCs need to be analyzed with molecular methods in each patient.

ctDNA, on the other hand, is much easier to isolate. When cells die, including cancer cells, some of the DNA they shed ends up in the [blood] plasma. This DNA in the circulation can be extracted from plasma and used for the characterization of the genetic makeup of tumor cells. In patients with advanced disease, tumor DNA can be collected even from a single vial of blood. As this is minimally invasive, multiple vials can be collected and the DNA extracted can provide important insights into the biology of the tumor.

More important, ctDNA may actually provide a more global — and therefore more accurate — picture of the cancer in the body. We have shown that at least in some patients, sequencing the ctDNA can capture all genetic alterations found in cancer cells in different parts of the body, because the cells dying and releasing DNA would come from all parts of the primary tumor and metastases.

What has made the study of ctDNA such a focus of interest recently?

The big change has been the introduction of next-generation sequencing, a new technology that allows us to sequence entire genomes of tumor cells to detect mutations with great accuracy. For example, we have a test here called MSK-IMPACT™, which can look for hundreds of cancer-related mutations at once with very high sensitivity. We have used this test to detect every clinically relevant mutation present in ctDNA from cells all over the body. Just a few years ago, this type of analysis would have pertained to the realm of science fiction.

Being able to detect the entire range of mutations could be of great help in planning therapy. If ctDNA sequencing can detect all mutations present in the different cancer cells from a patient, we have a better chance to select the optimal drug or combination of drugs for that particular patient.

How could analysis of ctDNA be used to monitor disease progression and treatment?

As with CTCs, there have been studies showing that disease progression can be tracked by monitoring ctDNA levels, particularly by how concentrated the ctDNA is in the blood. As cancer progresses, the levels go up. In addition, in the last two years, research here at MSK and elsewhere has shown that next-generation sequencing of ctDNA from the plasma of breast cancer patients could identify genetic alterations that arise at different stages of the disease and potentially tell us whether a tumor will recur.

When it comes to treatment, we are beginning to see that genomic analysis of ctDNA over time makes it possible to track how cancer cells evolve in response to therapy. We recently published a study demonstrating this approach in a single patient with advanced breast cancer that had spread to the liver and bone. Genetic analysis from the primary tumor had revealed a mutation in a gene called AKT, so the patient was enrolled in a clinical trial testing a targeted therapy. We also sequenced DNA from the liver metastasis and from plasma samples collected both before the patient started the trial and at multiple points after receiving the drug.

We saw that the mutations in the cancer cells changed as the patient first responded to the drug and then relapsed. The changes in genetic composition mirrored the response to the drug as indicated by PET scans of the tumor and metastases. Significantly, however, we detected increases in the amount of ctDNA in plasma that preceded the detection of disease progression by imaging analysis or biochemical tests.

Although this analysis was done in a single patient, it does establish an important proof of principle that we might use this technique to track new mutations as they arise in response to targeted therapy. Analyzing ctDNA could give us a fuller picture of disease progression and drug resistance.

What applications do you see for this technology in the near future?

The use of ctDNA from plasma is still in its infancy. We can’t lose sight of all that we don’t yet know. With circulating tumor cells, a lot of initial hopes have not yet been fully realized; however, the experience accrued with the analysis of CTCs may prove instrumental for the use of ctDNA in clinical practice. The lessons we have learned over the last decade about the development of molecular tests for treatment decision-making, coupled with technological developments, are cause for optimism that this type of liquid biopsy will lead to noninvasive — yet highly sensitive — ways of detecting and monitoring cancer in the body.

https://www.mskcc.org/blog/tumor-dna-bloodstream-may-yield-new-insights

This post is on Healthwise

Liquid biopsies: Tumour diagnosis and treatment monitoring in a blood test

Liquid biopsies are non-invasive blood tests that detect circulating tumour cells (CTCs) and fragments of tumour DNA that are shed into the blood from the primary tumour and from metastatic sites

• Date: 29 Sep 2014
• Author: Giuseppe Curigliano
• Affiliation: European Institute of Oncology, Milan, Italy
• Topic: Translational research / Basic science

Article extracted from the ESMO 2014 onsite newspaper.

This technology has enormous diagnostic and treatment implications for oncology and I believe it is poised to transform clinical practice. As an integral part of precision medicine, the importance of liquid biopsies was highlighted in a Special Session on Saturday, at which experts from around the world discussed its potential and limitations.

Guiseppe Curigliano, Congress Daily, Guest Associate Editor, European Institute of Oncology, Milan, Italy

So, what’s all the fuss about? Tumour genome sequencing to inform treatment decisions is already central to the management of many patients with cancer and I have witnessed this change the hallmark of cancer care. Tailored therapy relies on the identification of the correct molecular tumour target. Currently, tumour biopsy tissue, generally from the primary tumour, is used to determine molecular targets at a single time point, before treatment commences. These biopsies carry some risks for patients, they are painful, they are costly and, importantly, the process takes time. Also, given the complexities of tumour heterogeneity, both within a tumour and between a primary tumour and metastases, a tissue sample may not be a true representation of the molecular profile. A liquid biopsy, on the other hand, may capture the entire heterogeneity of the disease. What is more, tumour genotypes are notoriously unstable and prone to changes under selection pressure. In this regard, liquid biopsies offer what tissue biopsies cannot, due to risks to the patients and cost; the opportunity to take serial samples in order to monitor tumour genomic changes in real time. This will allow clinicians to ensure that the therapy they have selected, based on a particular molecular target, remains relevant and observe the emergence of any resistance. Instead of waiting for information from scans, we may be able to identify at an earlier stage if a treatment is not working and to spare the patient the unnecessary toxicity of a drug that no longer provides any benefit. At the same time, we may be able to observe if any new molecular targets appear that could be suitable for treatment. All this could help to provide patients with the right treatment for the right target without delay.

Liquid biopsies also present us with a unique opportunity to move forward with our understanding of metastatic disease development and they may help to identify signalling pathways involved in cell invasiveness and metastatic competence. Ultimately, at some point in the not too distant future, these tests will be used in the diagnosis of cancer. This will revolutionise cancer care, providing clinicians with rapid access to information on a molecular level at diagnosis, thereby optimising treatment choices.

In terms of samples, CTCs have been the most studied. While these cells are relatively rare and require sensitive collection and enrichment technology, they provide information at both the genetic and cellular level. However, cell-free tumour DNA (cfDNA) is emerging as an effective alternative to CTCs, with the benefits of easier collection and analysis. Today, a Poster Discussion Session on Trials and Tribulations in Oncology: Future Approaches (13.00 – 14.00, Pamplona) will feature two abstracts on cfDNA liquid biopsies: one on the use of serial next generation sequencing of cfDNA to monitor response and progression during administration of drugs in the phase I setting (Abstract LBA6) and another on the de novo detection of cfDNA in patients with refractory cancer (Abstract 1571PD). These studies should help us to build on our understanding of the type of information cfDNA-based liquid biopsies can give us.

We do know that standardisation will be a key factor in ensuring consistency between centres and in determining its clinical success. It is crucial that we standardise the assays used to evaluate cfDNA and also define the optimum sampling specimen (i.e. serum or plasma). In fact standardisation across the board would be ideal: blood collection, processing, storage, and DNA extraction, quantification, analysis and reporting of data. Future development of liquid biopsies will need to provide a cost-effective analysis, mainly identifying the genes known to be recurrently mutated in each tumour. Therefore, developing standardised methodologies for cfDNA analysis and validation in large prospective clinical studies is mandatory for the implementation of the liquid biopsy approach in the clinical management of cancer patients.

In the field of oncology, we see so many innovations come and go, without lasting impact. Will the promise of liquid biopsies be a clinical reality? It is hard for me to not to be excited about the benefits they can offer to patients and I believe that they will be invaluable to cancer research and treatment.

I would like to thank the Congress Daily Editorial Team of Evandro de Azambuja (Editor-in-Chief), Markus Joerger and Floriana Morgillo (Associate Editors) for giving me the opportunity to write this editorial. 

http://www.esmo.org/Conferences/Past-Conferences/ESMO-2014-Congress/News-Articles/Liquid-biopsies-Tumour-diagnosis-and-treatment-monitoring-in-a-blood-test

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Company Bets on Catching Cancer With 'Liquid Biopsy'

JAN 10 2016,

by MAGGIE FOX

Gene sequencing company Illumina is betting it can diagnose cancer in people long before they have any symptoms at all with a blood test called a liquid biopsy.

The San Diego-based firm launched a spinoff company Sunday named Grail, with obvious references to the "Holy Grail."

"The holy grail in oncology has been the search for biomarkers that could reliably signal the presence of cancer at an early stage," said Dr. Richard Klausner, a former director of the National Cancer Institute who's a member of the new company's board of directors.

The plan is to use Illumina's super-fast genetic sequencing technology to look for genetic material from tumor cells in peoples' blood long before they have any evidence of cancer. The test would check for genetic mutations known to be found in tumors.

Something similar is already done sometimes in people who already have cancer. The liquid biopsies are used to see how well cancer treatment is working.

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Some big names in investing and cancer researcher are signing on for the enterprise.

They include Amazon founder Jeff Bezo's Bezos Expeditions, Microsoft co-founder Bill Gates and Sutter Hill Ventures. Klausner; Dr. Jose Baselga, physician in chief at Memorial Sloan Kettering Cancer Center and president of the American Association for Cancer Research; and Dr. Brian Druker, director of the Oregon Health & Science University, have signed on to the advisory board.

"We hope today is a turning point in the war on cancer," said Jay Flatley, Illumina's chief executive and chairman of Grail.

"By enabling the early detection of cancer in asymptomatic individuals through a simple blood screen, we aim to massively decrease cancer mortality by detecting the disease at a curable stage."

"WE HOPE TODAY IS A TURNING POINT IN THE WAR ON CANCER."

It will be years before any such test could be designed, and it would have to be tested in thousands of people before regulators could consider approving it. Right now one of Illumina's whole-genome tests costs about $1,000, so it would be a pricey cancer screening test unless that cost can be brought down.

And while tumors are known to drop bits of genetic material into the blood, cancer experts caution that some early cancers may not secrete DNA fragments and require other types of detection.

Cancer is the No. 2 killer overall in the United States, but it's neck and neck with heart diseases.

Last week, the American Cancer Society projected that cancer would be diagnosed in close to 1.7 million Americans this year and that it would kill nearly 600,000. Most deaths are of people whose cancer had already spread before it was treated.

The U.S. Food and Drug Administration has been very skeptical of blood tests that claim to diagnose disease before people have symptoms.

In September, the FDA slapped Pathway Genomics over its "liquid biopsy" testthat claims to do what Grail proposes.

The FDA said the company had not shown the $699 test worked, warned that it "may harm the public health" and said the company hadn't applied for proper regulatory approval. 

http://www.nbcnews.com/health/cancer/company-bets-catching-cancer-liquid-biopsy-n493711

This post is on Healthwise