CAN GENETICS AND GENOMICS HELP DETECT EARLY CANCER AND MONITOR TREATMENT EFFECTIVENESS?
Many cancers, such as ovarian cancer and some kidney cancers, are typically only detected when they are relatively far advanced, because they may not be associated with noticeable symptoms in the earlier stages. One remarkable discovery in the past few years has been the finding that the DNA of solid tumor cells often can be found in the blood. This presumably occurs through the death of cancer cells whose contents are then released into the bloodstream. The discovery of this circulating tumor DNA (ctDNA) is important because it offers the possibility that a simple blood test might be used for detection of “silent” early cancers. Indeed, in a recent study designed to detect regions from 139 genes that frequently carry somatic mutations in non-small-cell lung carcinoma (NSCLC), ctDNA was detected in approximately 50% of patients with early (Stage I) NSCLC and in all of the patients with more advanced (Stage II–IV) NSCLC. This type of ctDNA assay is theoretically adaptable to many types of cancer, and it is likely that screening for ctDNA will become a standard component of early detection in the future for individuals known to be at risk for certain cancers. This raises the possibility that screening for cancer lesions using ctDNA in the blood may someday become routine. Consistent with this idea, it has been recently discovered that analysis of ctDNA in pregnant women for chromosome aberrations in the fetus, has revealed the presence of cancer DNA in the woman! Thus, it may be that expectant women will be among the first to receive this type of screening.
Other potential applications of ctDNA analysis are in patients already diagnosed with cancer—to monitor the effect of treatment, detect cancer recurrence, and even provide some insight into prognosis. Some studies have shown that after surgery to remove a tumor, the presence of residual ctDNA is associated with an increased risk of tumor recurrence. Thus ctDNA screening after surgery might be useful for identifying patients who should receive chemotherapy to eliminate remaining tumor cells. An increase in ctDNA in a patient whose cancer has been treated successfully could be an early sign of cancer recurrence. Sequence analysis of ctDNA provides a “real-time” look at the mutation profile of the tumor cells and could be helpful in determining prognosis. Finally, ctDNA could conceivably be used for tumor DNA analysis in cases where it is not possible to biopsy or not desirable to subject a patient to the risks of a tumor biopsy procedure. For example, for a patient with NSCLC who is in poor health and not responding to current treatment, and for whom lung biopsy is considered too high risk, analysis of ctDNA could be helpful for determining which somatic mutations are present and informing the decision about alternative treatment. Assessment of ctDNA is often referred to as a “liquid biopsy” because of its potential to perform many of the same functions as a conventional solid tumor biopsy.
Blood is not the only easily accessible material that has potential to be used to detect and monitor DNA released from solid tumor cells. Depending on the cancer, tumor DNA also may be found in stool, urine, and ascites (fluid accumulated in the abdomen in certain tumors). It is possible to detect colorectal cancer DNA in stool samples, and this is now the basis of a commercially available diagnostic test. The utility of urine DNA analysis for detection of early prostate cancer or bladder cancer is an area of active research.