As recently reported in the journal Science Translational Medicine, DNA snippets identified and extracted from the tumors of cancer patients are creating a new series of biomarkers which can be used in blood tests subsequent to cancer treatment to determine if cancer treatments are successful, or if traces of the tumor remain.
These fragments of damaged and rearranged DNA, which occur in tumors as a result of cancer but not in normal tissue, are being cited as virtual “red flags” to identify successful cancer treatments and the eradication of tumors.
The work was done by scientists and researchers at the Carlsbad, California-based Johns Hopkins Kimmel Cancer Center and Life Technologies, a biotechnology firm vested in understanding cancer and identifying new treatments.
The team used the “bad” DNA sequences to create biomarkers. Biomarkers, in medicine, are substances (proteins in blood, or, in this case, unusual DNA strings) whose presence, and concentration, reveal ongoing disease processes and their severity. For example, a large proliferation of white blood cells would indicate the presence of infection in the body.
To identify these genetic biomarkers, researchers at the Johns Hopkins Kimmel Cancer Center scanned the genomes of six cancer patients, looking for these large segments, or strings, of rearranged DNA. Then they developed blood tests based on each form of cancer, and each patient, which used the DNA clusters to identify how well patients were responding to cancer therapies, and if such therapies had eradicated the tumor(s).
Once the process is commercialized, oncologists and even family practitioners may be able to use the novel tests to identify tumor spread or recurrence much sooner than is possible with X-rays, CT scans, PET scanning and even MRI imaging.
The biomarkers obtained by the recent study came from four patients with both colorectal and breast cancers, and were developed by sampling both healthy tissue and tumor tissue. Genetic sequencing of multiple fragments, or strands, of DNA was achieved with massively parallel sequencing, which derives in principle from the multiprocessing principles applied in computing, where numerous CPUs achieve “cloud computing”.
The erratically arranged strands of DNA which form the basis for the cancer biomarkers are, according to Johns Hopkins Kimmel Cancer Center cancer specialist Luis Diaz, an “erosion of the genome” (which has also been cited as the cause of cancer by some specialists).
These genetic anomalies were discovered in at least four regions of each of the tumor samples, and their future benefit in identifying cancer (and the success of cancer treatments) is limited only by the cost of DNA sequencing, which can run as high as $5,000 per patient, compared to a CT scan costing about $1,500.
Fortunately, the cost of DNA sequencing is beginning to come down, to about $4,500, according to Mountain View, California-based Complete Genomics. In addition, and perhaps even more important than costs, is the fact that use of the revolutionary biomarker test may be able to eliminate post-surgical chemotherapy or radiation treatments, where the tumor has been successfully eradicated by surgical means alone. This would prevent the aftereffects of radiation and chemotherapy, which some patients find more debilitating that then original cancer itself.
Diaz also anticipates the novel biomarker genetic sequencing being used in initial cancer screenings, not only to determine the type (origin) of the cancer, but its spread to other organs. The only problem with a more universal application of the sequencing screening at this point, Diaz notes, is that the erratic DNA sequences vary from one person to another, with each individual having a very unique “fingerprint” even in terms of defective, or tumor-derived, DNA.
In spite of that, the study – which was jointly funded by the National Institutes of Health (NIH), the Bethpage, New York-based Lustgarten Foundation, and the National Colorectal Cancer Research Alliance – may eventually evolve to identifying markers which are common to many individuals, and the new technique – which the team calls PARE (personalized analysis of recombined ends) – marks the second really big step toward “personalized” cancer care, which has long been a goal of cancer researchers worldwide.
The first step, as cancer patients and their loved ones know, was the discovery of PSA, the prostate-specific antigen, closely followed by the CA125 test used to monitor ovarian cancer. In addition, cancers of the blood are already monitored by following their individual genetic signatures when testing patients for potential cures.
Meanwhile, rather than resting on their laurels, cancer researchers continue to look for more cancer biomarkers applying across broad population groups, or ways to use the approach to test larger groups.
Ultimately, Wellcome Trust Sanger Institute geneticist Daniel MacArthur (who writes the twice-weekly blog, Genetic Future) anticipates tests like the one developed at Johns Hopkins Kimmel Cancer Center will become the paradigm for cancer patients, delivering not only personalized cancer treatment and monitoring but the promise of more complete cures with less tinkering once a person’s “cancer fingerprint” is identified.
Sources: Genetic Future blog, UK Press, Business Week, CancerResearchUK