Highly specific biomarkers that provide information about cancer initiation, development, metastasis, and response to therapy have the potential to offer prognostic insight, while also facilitating the design and implementation of targeted treatments.
Because of the genetic complexity and diversity of cancer, these biomarkers are most useful when they identify a specific group of patients that would benefit from a highly targeted treatment, specifically optimized for their disease subtype. However, this is further complicated by the continued accrual of somatic mutations over time, for example, those driven by selective pressures exerted by the host immune system and external drug treatments. Therefore, it is necessary to regularly evaluate the biomarker signature of a cancer for changes over the course of treatment and during remission.
Cataloguing the genetic status of a given tumor traditionally involves carrying out sequencing analysis of fresh and/or archival biopsy specimens. However, there are several limitations to this approach. For example, tumor biopsies are often contaminated with the DNA of normal somatic cells, while the cancer cell population within a tumor tends to be genetically heterogeneous in nature.
The use of archival tissue samples, particularly if fixed and embedded in paraffin, can introduce further sources of error due to DNA degradation, which can interfere with analysis. Lastly, tumors can often develop in areas of the body difficult or impossible to access surgically, and can therefore not be assessed using this approach.