Liquid biopsies: Potential and challenges

Abstract

The analysis of tumor cells or tumor cell products obtained from blood or other body fluids (“liquid biopsy” [LB]) provides a broad range of opportunities in the field of oncology. Clinical application areas include early detection of cancer or tumor recurrence, individual risk assessment and therapy monitoring. LB allows to portray the entire disease as tumor cells or tumor cell products are released from all metastatic or primary tumor sites, providing comprehensive and real‐time information on tumor cell evolution, therapeutic targets and mechanisms of resistance to therapy. Here, we focus on the most prominent LB markers, circulating tumor cells (CTCs) and circulating tumor‐derived DNA (ctDNA), in the blood of patients with breast, prostate, lung and colorectal cancer, as the four most frequent tumor types in Europe. After a brief introduction of key technologies used to detect CTCs and ctDNA, we discuss recent clinical studies on these biomarkers for early detection and prognostication of cancer as well as prediction and monitoring of cancer therapies. We also point out current methodological and biological limitations that still hamper the implementation of LB into clinical practice.

PIK3CA Mutations as a Molecular Target for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer

“…Liquid biopsy using blood components to assess PIK3CA mutations in circulating tumor DNA (ctDNA) of patients with breast cancer has been reported by different studies (39). Multiple technologies have been employed to assess breast cancer ctDNA with high sensitivity and specificity, leading to assays that have been useful in clinical trials and are entering clinical practice (63). Using an ARMS allele-specific PCR and Scorpion probes, Board et al (64) were able to detect PIK3CA mutations in the vast majority (80%) of ctDNA samples from PIK3CA-mutated MBC but not in early breast cancer.…”

“…The main advantages of this procedure compared to conventional tissue biopsy are the noninvasive nature and repeatability. These allow for a timely followup, potentially overcoming spatial and temporal heterogeneity of tumor (63). On the other hand, a major limitation of this approach is the lower concentration of tumor-derived DNA compared to traditional tissue specimens.…”

Current Status of Circulating Tumor Cells, Circulating Tumor DNA, and Exosomes in Breast Cancer Liquid Biopsies

“…Although being promising, the implementation of such biomarkers into the clinical practice requires a better understanding of underlying shedding/releasing mechanisms, as well as dynamics and kinetics of the circulating tumor material. Moreover, there are still important technical issues that need to be resolved to improve reproducibility [ 139 ]. Therefore, in spite of the huge effort put in by the scientific community, the majority of liquid biopsy assays still lack evidence of clinical validity and, in particular, clinical utility.…”

Liquid Biopsy perspectives theranostics and personalized oncology

“…For these reasons, the majority of clinical decisions in the metastatic context tend to be based on biopsies of the primary cancer, and frequently do not represent the genetic profi le that allows establishing the treatment of the disease, particularly of metastases [6]. The current diagnosis of tumors is studied with a tissue biopsy, it is considered the gold standard, however, it has many limitations to have an accurate diagnosis, it determines its origin and genetic profi le, although it only allows studying a static and limited sample and eventually It is diffi cult to obtain, it has low sensitivity and precision, it does not allow determining heterogeneity or invasiveness, it is incompatible with longitudinal clinical follow-up, and it does not detect an early-stage tumor or residual tumors [7].…”