Personalised cancer treatment hope

Researchers have found a way to analyse the "fingerprint" of a cancer, and then use that fingerprint to track the trajectory of that particular tumour in that particular person.

"[This technique] will allow us to measure the amount of cancer in any clinical specimen as soon as the cancer is identified by biopsy," said study co-author Dr Luis Diaz, an assistant professor of oncology at Johns Hopkins University. "This can then be scanned for gene rearrangements, which will then be used as a template to track that particular cancer."

Diaz is one of a group of researchers from the Ludwig Centre for Cancer Genetics and Therapeutics and the Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Centre that report on the discovery in Science Translational Medicine.  This latest finding brings scientists one step closer to personalised cancer treatments, experts say.

How the study was done

"These researchers have determined the entire genomic sequence of several breast and colon cancers with great precision," said Katrina L. Kelner, the journal's editor. "They have been able to identify small genomic rearrangements unique to that tumour and, by following them over time, have been able to follow the course of the disease."

One of the biggest challenges in cancer treatment is being able to see what the cancer is doing after surgery, chemo or radiation and, in so doing, help guide treatment decisions.

"Some cancers can be monitored by CT scans or other imaging modalities, and a few have biomarkers you can follow in the blood but, to date, no universal method of accurate surveillance exists," Diaz stated.

Almost all human cancers, however, exhibit "rearrangement" of their chromosomes.

"Rearrangements are the most dramatic form of genetic changes that can occur," study co-author Dr Victor Velculescu explained, likening these arrangements to the chapters of a book being out of order. This type of mistake is much easier to recognise than a mere typo on one page.

But traditional genome-sequencing technology simply could not read to this level.

Breast cancer tumours analysed

Currently available next-generation sequencing methods, by contrast, allow the sequencing of hundreds of millions of very short sequences in parallel, Velculescu explained.

For this study, the researchers used a new, proprietary approach called Personalised Analysis of Rearranged Ends (PARE) to analyse four colorectal and two breast cancer tumours.

First, they analysed the tumour specimen and identified the rearrangements, then tested two blood samples to verify that the DNA had been shed into the blood, sort of like a tumour's trail of bread crumbs.

"Every cancer analysed had these rearrangements and every rearrangement was unique and occurred in a different location of genome," said Velculescu. "No two patients had the same exact rearrangements and the rearrangements occurred only in tumour samples, not in normal tissue," he noted.

"This is a potentially highly sensitive and specific tumour marker," Velculescu added. Levels of the biomarkers also corresponded with the waxing and waning of the tumour.

"When the tumour progresses, the relative amount of the rearrangement increases in the blood and goes down after chemotherapy," Diaz said. "It tracks very nicely with the clinical history of the tumour."

Cost will come down in future

The method would not be used for cancer screening and more research needs to be done to make sure PARE doesn't detect low-level tumours that don't actually need any treatment.

Although this approach is currently expensive (about $5,000 versus $1,500 for a CT scan), the authors anticipate that the cost will come down dramatically in the near future, making PARE more cost-effective than a CT scan.

Under the terms of a licensing agreement, three of the study authors, including Velculescu, are entitled to a share of royalties on sales of products related to these findings. - (HealthDay News, February 2010)