Biomarkers taking on greater importance

Suzanne Elvidge — Wed, 01 Feb 2012 07:23:47 -0500

You must believe that biomarkers are important because you are reading this newsletter, and, more to the point, you are reading this Editor's Corner. But to support what we believe, the importance of biomarkers is being validated by regulatory authorities and by guidelines.

Last week, the EMA issued a positive opinion on the use of an imaging-based biomarker to recruit patients into Alzheimer's disease clinical trials, the first time a biomarker of this type has been granted a positive opinion by a regulatory agency. This week, the National Institute on Aging and the Alzheimer's Association (NIA-AA) issued guidelines that include the use of biomarkers to support the postmortem diagnosis of Alzheimer's disease. Though diagnoses after death may seem of scant use to families, they are vital to support research, particularly of diagnostics.

Biomarkers have roles all the way through clinical development of therapeutics and diagnostics. They can be used to recruit patients into clinical trials, either by ensuring that the diagnosis is correct, as in the biomarker approved by the EMA above, or by selecting the appropriate subgroup that might respond to the drug. They can also help to monitor the progress of disease and the success (or failure) of the drug, and be used as a surrogate endpoint, substituting for a clinical endpoint to make a trial shorter, or the results clearer and more practically applicable. Of course, biomarkers are also important for physicians and patients by providing a route to personalized medicine.

So... that's the importance of biomarkers in a nutshell. As we look out over 2012 (or the rest of 2012--it is February already!) we look to another year of new breakthroughs in biomarkers, and their inclusion in more guidelines and recommendations. It should be an exciting year. — Suzanne Elvidge (email)

NINDS is close to launching its first NeuroNEXT neurobiomarkers study

Suzanne Elvidge — Wed, 01 Feb 2012 06:31:21 -0500

The National Institute for Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health (NIH), is getting ready to launch the first of the studies through NeuroNEXT, the National Network for Excellence in Neuroscience Clinical Trials, according to an article in The Lancet Neurology.

The first study will look at potential biomarkers in spinal muscular atrophy (SMA), an inherited disease that causes muscle weakness and loss. There is no known cure for SMA, and no drugs specifically approved for its treatment, and Repligen ($RGEN), a U.S.-based biotech company, is carrying out what is reported to be the first clinical trial for a therapeutic for SMA with its investigational agent RG3039, which increases levels of the missing protein.

NINDS created NeuroNEXT to support the development of studies and protocols to treat neurological disorders in children and adults through a network of 25 clinical centers, a central clinical coordinating center (CCC) and a central data coordinating center (DCC). The focus is on Phase II trials and biomarker validation studies, and the network hopes to support investigators who have not run studies before and link together sites to help researchers recruit patients for studies, which will be particularly important in rare diseases. The CCC and DCC will help with setting up and running trials, including creating a central institutional review board (IRB) and assisting with data analysis.

NINDS is looking for future biomarker and Phase II studies in any field of neurology, from academic institutions, charities and foundations, and the biopharma industry.

- see the article in The Lancet Neurology

Markers from breast could predict weight loss surgery outcome

Suzanne Elvidge — Wed, 01 Feb 2012 05:06:51 -0500

Gastric bypass surgery is only recommended for weight loss as a last resort after diet and exercise have failed. While the operations can be wildly successful, they don't work for everyone, there is a significant cost involved, and there are risks. Researchers at the University of North Dakota have spotted a couple of biomarkers that might help to pick out the women who could benefit the most.

Up to half of post-menopausal breast cancer deaths in the U.S. are linked to being overweight, and, as women lose weight, it seems that their risk is also reduced. The researchers looked at two biomarkers linked with breast cancer--adiponectin and prostate specific antigen (PSA)--in women who had gastric bypass surgery to see if there could be a link between the breast cancer markers and women's ability to lose weight.

All of the women in the study lost weight. The researchers found that low levels of prostate specific antigen from fluid taken from the nipple was linked to weight loss in post-menopausal women, and high adiponectin levels in the blood suggested weight loss in pre-menopausal women. The researchers recognize that this is a small and early study and needs further validation.

Even though the gastric bypass is by now common and routine surgery, there are still risks--surgery requires an anesthetic, which can cause problems in obese people, surgery requires people to radically change how they eat, and there is always the chance of infection. Further, the operation doesn't change any psychological pressures to eat. That said, gastric bypasses can save lives by cutting the risk of diabetes, stroke and heart disease, so a biomarker that suggests which patients it might work for, even if it means a needle in the breast, could be a step toward safer and more effective weight loss for at least a subgroup of women.

- see the abstract

Alzheimer's biomarkers panel not clear-cut after all

Suzanne Elvidge — Wed, 01 Feb 2012 03:24:47 -0500

Treating Alzheimer's disease early can delay symptoms and improve people's quality of life, and might even change the course of the disease, but it needs an accurate test. In 2007, it looked like we had one--a paper in Nature Medicine seemed to show that an 18-strong panel of biomarkers could identify Alzheimer's disease with pretty high accuracy and pick out the cases of mild cognitive impairment (MCI) that would lead to Alzheimer's disease. Recently, however, a team of Swedish researchers looked at the same panel of biomarkers, and found that they could not reproduce the results.

In the study, published in PLoS One, the researchers used the panel to screen people with Alzheimer's disease, depression or other types of dementia, and also looked at healthy controls. While the panel could separate out the people with Alzheimer's disease from the healthy controls (though only with low accuracy), it could not tell the difference between Alzheimer's disease and other dementias.

As the researchers said in the paper, these results show just how important it is to carry out independent validation of results in explorative biomarker studies, using different sets of patients and different laboratory techniques.

Testing cerebrospinal fluid is a fairly accurate test for Alzheimer's disease, but a lumbar puncture is uncomfortable and invasive. A simple blood test for Alzheimer's is one of the holy grails of diagnostics research, but at the moment it still seems a few steps away.

- see the article in PLoS One
- check out the abstract in Nature Medicine

Genetic test could up outcomes after lung cancer surgery

Suzanne Elvidge — Tue, 31 Jan 2012 15:26:02 -0500

When patients present with early-stage non-small-cell lung cancer, doctors assess the tumors by looking at their size, location and appearance, and use this information to decide what to do after surgery--whether to use chemotherapy or watch and wait. Knowing who would benefit from extra treatment could improve their chance of survival, and a genetic test in development with researchers at the University of California-San Francisco in collaboration with Pinpoint Genomics may aid this process.

Around 35 percent to 45 percent of people with early stage lung cancer die within 5 years if the disease recurs, often because they harbor tiny and undetectable metastatic cancers. Being able to find these and treat them could improve their chance of survival. UCSF's 14-gene test detects the genetic biomarkers associated with these metastatic cancers.

In two large clinical trials, the researchers assessed the genetic test against tissue samples from 433 people in the U.S. and 1,006 people in China with early-stage lung cancer. The test was able to predict, correctly, the odds of death within 5 years of lung cancer surgery as low, medium or high, with 71 percent of people classified as low risk in both trials. The study in China was reported to be the first major clinical trial under the auspices of the China Clinical Trials Consortium (CCTC), which was founded with support from UCSF.

"It's quite exciting," said Dr. David Jablons, the Ada Distinguished Professor in Thoracic Oncology and leader of the Thoracic Oncology Program at the Helen Diller Family Comprehensive Cancer Center at UCSF. "This has the potential to help hundreds of thousands of people every year survive longer."

According to the researchers, these are the two largest clinical studies ever conducted on the molecular genetics of lung cancer. The next step is to conduct a large clinical trial, selecting people classified as high risk and assigning them to either treatment or the watch and wait method. This genetic test, if it makes it through to the market, could help physicians predict the outcome for patients and decide who might benefit from extra treatment after surgery, potentially saving lives.

- read the UCSF press release
- see the abstract in the Lancet
- check out the article in Medical News Today

MRS can detect brain tumor biomarker

Suzanne Elvidge — Sun, 29 Jan 2012 15:12:41 -0500

Many patients with a form of brain cancer called glioma have mutations in two genes that code for enzymes, IDH1 and IDH2. These changes result in increased levels of a compound called 2-hydroxyglutarate (2HG), seen in 80% of low- and intermediate-grade gliomas, and this biomarker can be detected using magnetic resonance spectroscopy (MRS). In a technical report published in Nature Medicine, researchers from University of Texas Southwestern Medical Center confirmed the technique's efficacy by analyzing tumors from 30 patients. They suggested that 2HG could be a valuable diagnostic and prognostic biomarker, as patients with this mutation tend to have better outcomes. Article | Abstract

New biomarker panel could support colorectal cancer diagnosis

Suzanne Elvidge — Fri, 27 Jan 2012 14:48:27 -0500

Colorectal cancer is the second most common cause of cancer death in the West, linked largely to a love of booze, red meat and high-fat food combined with a lack of exercise. Further, symptoms are of the kind that people often don't want to talk to their doctors about--such as changes in "bowel habits"--and screening is either costly, invasive or not very specific. All the more reason why there's a need for a panel of biomarkers.

In a study published in BMC Cancer, a team of Spanish researchers analyzed the genetic material from tumors at different stages and compared these against non-tumor samples. They found genes directly involved in cancer progression, creating a genetic biomarker panel of 7 genes that should be able to discriminate accurately between non-cancerous and cancerous samples.

A diagnosis of colorectal cancer need not be a death sentence, and the use of biomarkers could differentiate the disease from others that mimic the symptoms, meaning that patients could be treated much earlier and have a better potential outcome. Future work is planned to look at each stage of disease, and according to the researchers, this biomarker panel could constitute the basis of a new tool with strong potential for colorectal cancer diagnosis.

- see the paper (.pdf)

Researchers fingerprint head, neck cancer for better diagnostics

Suzanne Elvidge — Wed, 25 Jan 2012 07:40:03 -0500

Aggressive cancer treatment can be associated with a lot of side effects, but is often essential if the cancer is going to be life-threatening. Knowing how fast a cancer will progress is therefore very useful in helping physicians (and patients) decide how aggressively to treat the tumor. A genetic marker, known as miR-375, might help to meet this need.

Changes in microRNAs (miRNAs), short noncoding stretches of genetic material, seem to have turned up with just about every cancer type examined so far. Researchers from the Albert Einstein College of Medicine have compared levels of miRNAs from samples of head and neck squamous cell carcinoma (HNSCC) and normal tissues from the same patients to find those that were the most altered, to see if they could act as potential biomarkers.

Of all the miRNAs assessed, miR-375 showed the most significant differences between the reduced levels in the cancerous cells compared with the levels in the normal cells. The researchers linked these results with patient outcomes, and found that the larger the difference in miR-375 between normal and cancer cells, the more likely there would be a reduced chance of survival and an increased risk of metastasis. The results were published in the American Journal of Pathology.

"Previous efforts to identify biomarkers for guiding treatment of head and neck cancer have not developed anything clinically useful for patients," said Geoffrey Childs, Ph.D., professor of pathology at Einstein and co-senior author of the paper.

The survival rate at 5 years for head and neck cancer is around 50% and this hasn't altered much in 40 years. This biomarker could increase this survival rate and improve quality of life, not only by helping out patients that will respond, but by avoiding aggressive treatment in those patients that won't.

- read the press release
- see the abstract in American Journal of Pathology