Cancer DNA: The New Frontier for Preventing and Curing Cancer

By Jesica Levingston Mac Leod, PhD

 

DNA Biomarkers are the hot topic in oncology right now, and the more precise, easy and effective they may be to detect cancer, the better.  This cutting edge technique has its origins in the discovery that fetuses shed fragments of DNA into the bloodstreams of the mothers, so do normal and cancer cells. The strategy to search for the most accurate “bar code” for each type of cancer is been approach from a bunch of oncologists around the world.

Researchers from the National Cancer institute, MD, published this month in the Lancet, a correlative biomarker study for lymphoma. In the study publish by Roschewski and col., they detected circulating tumor DNA encoding the clonal immunoglobulin gene sequence (VDJ) in the serum of patients with diffuse large-B-cell lymphoma. The VDJ immunoglobulin genes contain unique sequences that are markers of clonality. Malignant cell VDJ gene sequences could be detected in the serum of patients with diffuse large B-cell lymphoma and used to predict clinical disease recurrence after treatment. For this, they used next-generation DNA sequencing to analyze cell-free circulating tumor DNA in patients assigned to one of three different treatment protocols during a period of 20 years. They concluded that “Surveillance circulating tumor DNA identifies patients at risk of recurrence before clinical evidence of disease in most patients and results in a reduced disease burden at relapse. Interim circulating tumor DNA is a promising biomarker to identify patients at high risk of treatment failure.”

Earlier this year, Hyman and col., reported the analysis of a biomarker (the mutant BRAF(V600E)) in 2 systemic histiocytic disorders characterized by accumulation and infiltration of histiocytes in multiple tissues of the body, leading to organ compromise. These researchers from Memorial Sloan Kettering Cancer Center, New York, showed that in plasma and urinary samples cell free DNA provides a reliable method to detect the mutation that is a biomarker for these disorders, and it can monitor response to therapy in these disorders.

In Australia, the group of doctors  Tie, Cosgrove and col., identified and validated 3 protein-based biomarkers in independent cohorts of colorectal cancer (n = 145 and n = 197), which could be translated to a reliable, non-invasive blood-based screening test. The biomarker “winners” were selected by Elisa kits, and they are the following proteins: Insulin like growth factor binding protein 2 (IGFBP2), Dickkopf-3 (DKK3), and Pyruvate kinase M2(PKM2). (3) Anyways, this article is bout DNA markers: So, in a follow up study Tie and col. detected circulating tumor DNA in a high proportion of treatment naïve metastatic colorectal cancer patients. Moreover, they described that early changes in circulating tumor DNA during first-line chemotherapy predict the later radiologic response.  On other notes, they also reported that the intake of aspirin is not associated with improvements in survival in colon cancer patients, yeah, bad news for the daily aspirin takers.

Studying the blood samples of healthy elders (“wellderlies”, adults age 80 plus), the team lead by doctor Eric Topol, at the SCRIP center, is trying to find the immune response that attacked and effectively destroyed cancer cells. There is a high probability that these healthy elders had had abnormal cell/cells in their bodies at some point of their lives, which they attacked and destroyed, generating immune memory and powerful anti-cancer antibodies. In fact, a member of the team, Doctor Brunie Felding, had discovered that one of the proteins recognized by “wellderly” antibodies was Apolipoprotein E, suggesting that antibodies against this protein may help develop a targeted therapy against highly-expressing ApolipoproteinE cancers.

These new discoveries, plus the recently  FDA approval of three new immuno-oncology therapy drugs, called PD-1 inhibitors,  are bright examples of the importance of cancer research funding and support from the public to the government officers.

One of the most influential bioinformaticians/molecular biologists, Dr. George Church, genetics professor at Harvard, thinks that “the DNA is the ultimate computer code and we are all computer programmers”. Therefore, the study of the DNA fragments can help to solve multiple problems… it is working for cancer therapy, and it could be useful to treat even the most common disease: aging.