Cancer Genomics Treatment
Cancer is caused by changes in a once-normal cell, which accumulates genetic damage and mutations in the cell’s “instruction book”, the DNA, causing the cell to grow and multiply uncontrollably. Today, we know much about the many mutations which can contribute to cancer, some mutations which can be inherited, as well as the many gene mutations which arise randomly and due to environmental exposures. Increasingly, these mutations can be targeted by approved drugs as well as dozens of therapeutics currently in development around the world.
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An accurate snapshot of the current state
It has been known for decades that DNA from cells can escape and circulate as free-floating DNA, so-called cell-free DNA (cfDNA), in the bloodstream. In a cancer patient, the mutated DNA from tumor cells also escapes into the blood stream. This happens in proportion to the number of tumors and cancer cells in the body. In this case the DNA is called circulating tumor DNA (ctDNA). All circulating DNA is rapidly degraded to short fragments. Therefore, the quantity of ctDNA at a given time point provides a precise snapshot of the current tumor burden. Importantly, the ctDNA also makes its way into other bodily fluids such as the urine, and depending on the location of the tumor, also into saliva/sputum, cerebrospinal fluid, and other secretions. Together, the interrogation of these fluids as a source of diagnostic specimens is known as the minimally-invasive “liquid biopsy”. Until recently, however, the technology has not existed to accurately and reliably distinguish the ctDNA from the normal-cell-derived cfDNA.
Our research as well as the work of others has indicated that ctDNA is an excellent cancer biomarker. The reasons are manifold:
- ctDNA is released by all tumors in the body, thus a blood sample will provide a diagnostic result for all cancer clones at the same time in a single test;
- The quantity of ctDNA is proportional to the number of cancer cells and tumors in the body, therefore ctDNA quantity gives a read-out of the total amount of cancer in a patient;
- All types of DNA alterations such as the gene mutations and chromosomal rearrangements present in the patient’s cancer are represented in the ctDNA, thus ctDNA gives an accurate picture of the complete genetic makeup of the cancer including information on the mutations that are drug targets;
- Liquid biopsy sampling, such as a blood draw, is a simple and inexpensive procedure that can be performed by any medical personnel, can be easily repeated at multiple time points, and the samples obtained can be handled and shipped at room temperature.
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