Washington: In the usual cancer biopsy, a surgeon cuts out a piece of the patient’s tumor, but researchers in labs in the US are testing a potentially transformative innovation. They call it the liquid biopsy, and it is a blood test that has only recently become feasible with the latest exquisitely sensitive techniques. It is showing promise in finding tiny snippets of cancer DNA in a patient’s blood.

The hope is that a simple blood draw — far less onerous for patients than a biopsy or a CT scan — will enable oncologists to quickly figure out whether a treatment is working and, if it is, to continue monitoring in case the cancer develops resistance. Failing treatments could be abandoned quickly. “This could change forever the way we follow up response to treatments but also the emergence of resistance for really early diagnosis,” said Dr. Jose Baselga of Memorial Sloan Kettering Cancer Center.

Researchers caution that more evaluations of the test’s accuracy and reliability are needed. So far, there have been only small studies in particular cancers, including lung, colon and blood cancer. But early results are encouraging. A National Cancer Institute study published this month in The Lancet Oncology, involving 126 patients with the most common form of lymphoma, found the test predicted recurrences more than three months before they were noticeable on CT scans. The liquid biopsies also identified patients unlikely to respond to therapy.

Oncologists who are not using the new test say they are looking on with fascination. “Our lab doesn’t do it, but we are very interested,” said Dr. Levi Garraway of the Dana-Farber Cancer Institute. “It’s exciting,” he added. “It’s a top priority.”

Researchers are finding out things about individuals’ cancers that astonish them. Mary Susan Sabini, a fifth-grade teacher from Gardiner, NY, has lung cancer that resisted two attempts at chemotherapy and a round of radiation. Her doctors at Sloan Kettering saw cancer DNA in her blood when she began taking an experimental drug in October that was her last hope.

Indian-origin scientist develops app that helps in cancer research

A new mobile app developed by an Indian-origin scientist allows your smartphone to help conduct research on breast cancer and Alzheimer’s while the device is at rest and charging.

The Folding@home mobile app is an extension of the Folding@home distributed computing project launched by Vijay Pande, a professor of chemistry at Stanford University, in collaboration with Japanese corporate giant Sony in 2007.

The new app, Pande said, expands on the original programme, which has already simulated the structure of dozens of proteins and led to many important discoveries related to physiology and medicine.

Proteins are produced as linear ribbons of molecules, and then snarl up like a ball of yarn, a process known as ‘folding.’

The configuration of that snarl is intensely critical to the protein’s ability to function properly.

If a mutation or other malfunction shifts a few pieces slightly out of place, the protein’s function will be impaired.

One of the best ways to study protein configurations is to predict the folding process using computers.

In 2007 Pande and Sony launched the Folding@home project, tapping a distributed network of computer and Playstation 3 GPUs (graphics processing units) to simulate protein folding in their downtime.

The desktop programme counts roughly 150,000 users and can provide full models of specific proteins — which are submitted for simulation at researchers’ request — to scientists in weeks.

The new app is designed to run only when your phone is not in use, most likely as it charges while you sleep.

Once you activate your phone, the application will shut down and seamlessly hand the simulation to another phone that is not in use, which Pande said should maximize the network’s capacity.

Currently Pande has chosen for the application to focus on simulating several configurations of a kinase protein involved in breast cancer.

Scientists have found that individual breast cancer patients respond more favourably to different drugs, and they believe that this reaction might be due to individual differences in how this kinase is configured.

Pande said that simulating a dozen or so possible configurations of the kinase, and then testing how these fit with a suite of drugs, could help identify better courses of treatment.

The kinase takes about 300,000 nanoseconds to fold, and a smartphone can simulate about one nanosecond per day, Pande said. If 10,000 phones work eight hours a day, the project could be complete in three months.

Once the enrolled smartphones simulate the proteins with enough specificity to be useful to scientists, the app will launch a new project, this one to investigate proteins associated with Alzheimer’s disease.

Four days later, the cancer DNA shards had vanished, a sign, the doctors hoped, that the treatment was working. But they dared not tell her the good tidings. The blood test itself was so new they were afraid to rely on it.

Within weeks, Sabini began to breathe easier. Months later, she had a CT scan, an X-ray test that uses a computer to assemble detailed images of slices of tumor tissue. It confirmed her tumors were shrinking.

“Every cancer has a mutation that can be followed with this method,” said Dr. David Hyman, the oncologist at Sloan Kettering who is leading the study of the experimental drug Ms. Sabini takes. “It is like bar coding the cancer in the blood.”

The idea for the test grew out of a discovery made years ago about fetuses: They shed little pieces of DNA into the bloodstreams of mothers-to-be. It turned out that all growing cells, including tumors, shed tiny DNA fragments.

But finding those minuscule bits of DNA, floating in a sea of other molecules, is not easy. They remain in circulation for just a couple of hours before they are metabolized. And the detection method became useful only when cancer researchers, using advanced methods for DNA sequencing, found hundreds of mutations that could serve as bar codes for cancers and developed the technology for finding a snippet of DNA.

The standard methods of assessing a treatment’s effectiveness have serious drawbacks. Doctors routinely monitor patients for symptoms like pain or shortness of breath, but some people do not have any. In those who do, it can take time for such symptoms to wane — the tumor can die, but the body has to heal.

Patients often have scans to determine if tumors are shrinking, but it can take weeks or months before a tumor looks smaller on a scan, in part because a scan shows not just the cancer but also connective tissue, immune system cells and scars at the site. Doctors can be fooled into thinking a tumor is present when, in fact, it is gone.

“When you are treating a patient — and we see this many times — your treatment is quite effective but there is some residual lesion on a scan,” Dr Hyman said. “You take the patient to surgery for a biopsy, and all you see is scar tissue. There is no visible cancer there.”

The blood tests also allow frequent monitoring of tumors as they spread and mutate or develop resistance to treatment. The only other way to know is with biopsies.

“I cannot do a weekly liver biopsy and see how things are going,” Dr Baselga said. “But I can do a blood test every week.”

Metastasis is the spread of cancer from one organ to another. After a single cell in tissue gets progressively damaged, and produces a cancer stem cell with a malignant phenotype, it undergoes an uncontrolled abnormal mitosis creating a tumor. (Getty Images)

Another possible application — early diagnosis of cancer — is trickier. If a blood test showed cancer DNA, what would that mean? Where is the tumor, and would it help to find and treat it early? Some cancers stop growing or go away on their own. With others, the outcome is just as good if the cancer is found later.

One early use for DNA blood tests may be helping doctors decide which patients with Stage 2 colon cancer need chemotherapy. Eighty percent of patients with these large tumors that have not spread outside the colon are cured by surgery alone; the rest have recurrences. Six months of intense chemotherapy reduces the risk the cancer will return, but there is no way to predict who needs the treatment.

Two Australian scientists, working with Dr. Bert Vogelstein of Johns Hopkins, wondered if a cancer DNA blood test might be predictive. They began with a study of 250 patients, looking for cancer DNA in blood after surgery. The tumors recurred in 80 percent of those with cancer DNA in their blood but only 6 to 8 percent of those whose blood did not have detectable cancer DNA.

Now the Australian researchers, Dr Jeanne Tie and Dr Peter Gibbs of the Walter and Eliza Hall Institute of Medical Research, are starting a study of 450 patients randomly assigned to have the blood test or not. Those who have it will get chemotherapy if the test finds cancer DNA. Those who do not have the blood test will get usual care, whatever their physician prescribes.

The patients will be told their blood test results, although the investigators worry how some will react.

“If you find DNA and tell the patient there is a very high risk of recurrence, that creates a lot of anxiety,” Dr Gibbs said. “And we are not sure chemotherapy will be helpful.”

The blood test, they hope, will answer that question.

“This will be the first real test of whether circulating tumor DNA can be clinically useful,” Dr Vogelstein said.