Evaluation and consequences of heterogeneity in the circulating tumor cell compartment

Abstract

A growing understanding of the molecular biology of cancer and the identification of specific aberrations driving cancer evolution have led to the development of various targeted agents. Therapeutic decisions concerning these drugs are often guided by single biopsies of the primary tumor. Yet, it is well known that tumors can exhibit significant heterogeneity and change over time as a result of selective pressure. Circulating tumor cells (CTCs) are shed from various tumor sites and are thought to represent the molecular landscape of a patient's overall tumor burden. Moreover, a minimal-invasive liquid biopsy facilitates monitoring of clonal evolution during therapy pressure and disease progression in real-time. While more information becomes available regarding heterogeneity among CTCs, comparison between these studies is needed. In this review, we focus on the genomic and transcriptional heterogeneity found in the CTC compartment, and its significance for clinical decision making.

ERCC1-expressing circulating tumor cells as a potential diagnostic tool for monitoring response to platinum-based chemotherapy and for predicting post-therapeutic outcome of ovarian cancer

“…The broad heterogeneity of CTCs in the blood of cancer patients, including ovarian cancer, has already been indicated by several independent reports [25–27]. We may hypothesize that ERCC1-expressing CTCs play a dominant role during the course of the disease, which is corroborated by the fact that the rate of exclusively ERCC1-positive CTCs did not decrease after platinum-based chemotherapy.…”

Tracking cancer progression: from circulating tumor cells to metastasis

“…Single-cell analyses have revealed that CTCs often comprise a heterogeneous population of cells. Logically, this heterogeneity may reflect the extent of intratumor heterogeneity (ITH) [65][66][67][68][69][70] and may have important implications for prognosis and resistance to therapy. Indeed, a recent study of archived samples from patients with metastatic breast cancer found 85% concordance between CTCs and metastatic sites in terms of mutations and copy-number profile [71].…”

The potential for liquid biopsies in the precision medical treatment of breast cancer

“…In addition there are a variety of NGS platforms available including second generation, sequencing of an ensemble of DNA molecules with wash-and-scan techniques and third generation, sequencing single DNA molecules without the need to halt between read steps, whether enzymatic or otherwise 145 (Table 3) 136,[146][147][148][149][150][151][152][153][154][155][156][157][158][159][160] .…”