Abstract

Clinical Applications of Liquid Biopsies

Klaus Pantel, Professor and Founding Director, University Of Hamburg

The analysis of circulating tumor cells (CTCs) and tumor cell products (DNA,RNA, extracellular vesicles) released into the blood may provide clinically relevant information as “liquid biopsy” and provide new insights into tumor biology (Pantel & Alix-Panabieres, Nature Rev Clin. Oncol. 2019). Various technologies have been developed over the past 10 years which include label-dependent assays based on the expression of tumor-associated cell surface antigens and label-independent assays based on physical properties of tumors cells distinct from the surrounding leukocytes (Pantel & Alix-Panabieres, Nature Rev Clin. Oncol. 2019). After detection CTCs can be further analyzed at the DNA, RNA and protein level to obtain global information on tumor biology and targets relevant to cancer therapy (Pantel & Alix-Panabieres, Nature Rev. Clin. Oncol. 2019). In particular, microRNAs control various genes and pathways that impact the biology of tumor cells (Anfossi, Bababayan, Pantel, Calin, Nature Rev. Clin. Oncol. 2018).

Liquid biopsy analyses with validated platforms provides reliable information on early detection of cancer, identification of cancer patients at risk to develop relapse (prognosis), and it may serve to monitor tumor evolution, identify therapeutic targets or mechanisms of resistance on metastatic cells. Metastatic cells might have unique characteristics that can differ from the bulk of cancer cells in the primary tumor currently used for stratification of patients to systemic therapy. Moreover, monitoring of blood samples before, during and after systemic therapy (e.g., chemotherapy, targeted therapy or immunotherapy (Hofman et al., Ann. Oncol. 2019)) might provide unique information for the future clinical management of the individual cancer patient and might serve as surrogate marker for response to therapy.

In conclusion, the liquid biopsy analysis can be used to improve the management of individual cancer patients and contribute to personalized medicine. CTCs are complementary to other liquid biopsy biomarkers (Alix-Panabieres & Pantel, Cancer Discovery, 2016; Bardelli & Pantel, Cancer Cell 2017). Validation of liquid biopsy assays is essential and currently performed by the EU/IMI consortium CANCER-ID (www.cancer-id.eu).