Solid cancer tumors typically are diagnosed, graded, and staged using tissue biopsy in which all or part of a neoplasm—usually the primary tumor—is removed for histological examination and genetic and molecular analysis, writes Curtis Balmer, PhD, in the July issue of CLN.
While tissue biopsy provides important diagnostic and therapeutic information, it has several inherent drawbacks that limit its clinical utility. To overcome these, new biopsy techniques are being developed and evaluated, Balmer indicates in the article.
A particularly promising method is liquid biopsy, which exploits the presence of tumor cells in the bloodstream. As Bert Gold, PhD, FACMG, a staff scientist with the National Cancer Institute’s Center for Cancer Research, explained, “Circulating tumor cells are cells of origin from a usually solid tumor that have gone into the general circulation and can be viewed in peripheral blood.” Enthusiasm for this approach reflects its potential to sidestep the limitations of tissue biopsy. For example, tissue biopsy is invasive, poses some risk to patients, and is often painful, slow, and costly, and therefore not practical for closely monitoring a patient’s disease progression and treatment response.
In contrast, liquid biopsy requires only a simple blood draw; therefore, it poses little risk and is quick, painless, and cost-effective. As such, it may enable clinicians to closely monitor disease progression and treatment response in near-real time without unduly burdening the patient.
Indeed, liquid biopsy may facilitate more personalized care for each patient. The success of this approach, however, depends on isolation and detection of circulating tumor cells (CTCs), a challenging task given their rarity—about 1 to 10 CTCs per mL of whole blood.
Numerous isolation and detection strategies are being developed and investigated for clinical use. In general, these isolate CTCs based on distinguishing biological and physical properties. Biological strategies primarily use antibodies against tumor-specific cell surface antigens such as epithelial cell adhesion molecule (EpCAM) to identify CTCs. Typically these assays utilize antibody-coated magnetic beads that bind with the targeted antigen. Labeled CTCs are then removed from suspension with a magnet.
Molecular assays are also being developed that isolate CTCs based on gene expression, which is analyzed using total CTC RNA and reverse transcription polymerase chain reaction techniques to amplify tumor- and epithelial-specific markers. CTC isolation, detection, and molecular characterization systems are being investigated not only in breast, prostate, and colon cancers, but also pancreas, lung, skin, and head and neck cancers, among others.
While remarkable progress is being made in elucidating CTC biology, and numerous groups are aggressively pursuing development of clinical CTC assays, fundamental questions must be answered before CTC analysis can be adopted into routine practice.
Read more about the potential for CTCs to detect cancerous tumors in the July issue of CLN.