Biomarkers crucial to track cancer

Living cells have precisely controlled growth and multiplication mechanisms. Occasionally they get disturbed due to many reasons. The result may be uncontrolled multiplication of cells forming cancer.

Cancer cells exhibit widespread structural changes in their chromosomes. Bloodstream flowing past a cancerous tissue carries tiny fragments of genetic material shed by the tumour. These are tumour-specific and are useful as personalised biomarkers. A special blood test helps to characterise such biomarkers and to verify the effectiveness of treatment.

Researchers from John Hopkins Kimmel Cancer Centre, Baltimore and Life Technologies Corporation, USA, have developed a new method for tracking cancer by identifying the personalised biomarkers shed from tumour DNA (Science Translational Medicine, 24 February 2010). It depends on the Personalised Analysis of Rearranged Ends or PARE approach, using the latest DNA sequencing technology.

It provides an accurate and specific way to monitor tumours, by searching for the genetic trace material trail left by residual cancer cells after surgery or during drug therapy. The most important finding is that each tumour has a unique rearrangement of genomes.

When a surgeon removes a tumour, he is not sure whether he removed it entirely or not. For effective treatment, he is forced to give chemotherapy or radiotherapy. Not any more, if biomarkers are assessed before treatment. Now he can monitor tumour response to specific therapies, detect residual disease after surgery and organise long-term clinical management. At $5,000, the test is too costly. However, the cost will come down in the future. Researchers have applied the method on six cancer patients.

They claimed that there is no technology to determine whether a surgeon has inadvertently left some stray tumour cells.

What about Positron Emission Tomography or PET scan which pinpoints cancer cells? (Cancer cells metabolise sugar at higher rates than normal cells, and a radiopharmaceutical such as fluoro-deoxyglucose is drawn in higher amounts to cancerous areas. Cancer cells can thus be pinpointed by using Fluorine 18, a radioactive atom as a tracer.)

PET scans to monitor tumours

“The PET scans are fantastic tools to help stage and monitor a variety of tumours,” Dr Louis Diaz Jr, one of the researchers conceded. “However, the limit of detection is about one cm in diameter. There are billions of tumour cells in a tumour of that size.

Unfortunately after surgery, there is no tumour evident by any imaging technique and we need markers that are sufficiently sensitive to detect otherwise undetectable or occult micrometastases. This technology offers such a solution for cancer patients,” Dr Diaz Jr responded to an e-mail query.

As the sensitivity of the test is very high, there is a possibility that symptomless patients may also use the test to discover latent tumours. This may lead to needless worry among the persons who are positive to the tests, though the hidden tumours may never cause any fatal consequences. What is the reaction to such a possibility?

“At this time, we can only monitor patients with a history of biopsy-proven cancer and not otherwise healthy patients,” Diaz clarified.

Do the researchers think that the entire exercise may become technology driven and push up the cost of healthcare?

“We do not believe this will be a useless test that drives up the cost of healthcare; rather we believe that PARE will be able to more clearly delineate which patients would benefit from additional chemotherapy and which patients may be able to avoid it. This may, in part, help focus expensive therapeutics to patients who would benefit and protect patients who do not need chemotherapy,” he contended.

Comparison of costs

The authors compare the cost of the technique with that of a CT scan. Is it not more meaningful to compare their method with a PET scan?

Dr Diaz noted that while imaging studies are great for staging and monitoring those patients with active disease, they are not sufficiently sensitive to pick up micro-metastatic disease not readily detectable by any imaging modality. In the late stages, cancer cells get separated from the primary tumour and move away from it through blood as a carrier. They grow at the points where they collect, and this phenomenon is called metastasis.

“In these cases, imaging adds very little information and only contributes to cost.  A blood-biomarker, like PARE, will be able to detect cancer when present and not visible on any PET, CT or MRI scan,” he added.
Identifying how effective is a mode of treatment may offer renewed hope to cancer patients.

(The author is a Raja Ramanna Fellow, Department of Atomic Energy)