Cancer Liquid Biopsy: Is It Ready for Clinic?

Abstract

The management of cancer relies on a combination of imaging and tissue biopsy for diagnosis, monitoring, and molecular classification-based patient stratification to ensure appropriate treatment. Conventional tissue biopsy harvests tumor samples with invasive procedures, which are often difficult for patients with advanced disease. Given the well-recognized intratumor genetic heterogeneity [1], the biopsy of small tumor fragments does not necessarily represent all the genetic aberrations in the tumor, but sampling the entire tumor in each patient is not realistic. Moreover, tumors evolve all the time from local to advanced disease and by adapting to selective pressure from treatment.

Liquid biopsies for hepatocellular carcinoma

“…1,2,7 The high mortality rate of HCC is attributable to lack of effective early detection tools, limited treatment options, and high-frequency recurrence. 8–10 Although liquid biopsies have shown promising applications already in clinic for several cancers such as colorectal carcinoma, breast cancer, and lung cancer 11–16 in predicting response to therapy and monitoring relapse, their relevance in clinical application for liver cancer is limited. Due to the shedding of ctDNA into circulation by the microcirculation of discontinuous sinusoids (fenestrated capillaries with intercellular gaps and a fragmented basement membrane) in the liver, liver cancer should be particularly suitable for liquid biopsy for cancer genetics for precision medicine once more treatment options become available and for drug development.…”

Urine-Based Liquid Biopsy for Nonurological Cancers

“…Among available body fluids, blood is certainly the most direct body fluid for detection of ctDNA with most extensive studies on clinical applications in cancer liquid biopsy (Forshew et al, 2012;Crowley et al, 2013;Diaz and Bardelli, 2014;Franovic et al, 2017;Kwapisz, 2017;Malapelle et al, 2017;Pan et al, 2017;Wan et al, 2017;Hench et al, 2018). However, urine provides unique benefits as a truly noninvasive liquid biopsy; it can be collected, stored, pro-cessed, and shipped more easily than blood.…”

Possible application of circulating free tumor DNA in non-small cell lung cancer patients

“…Targeted NGS is recently used for the non-invasive detection of genetic alterations in lung cancer patients ( Table 2). There are three tests (Guardant360, FoundationACT and OncotypeSEQ) that, though not still FDA approved, have demonstrated good accuracy when validated with clinical samples (59). Among them, Guardant360 is the one most commonly used by the oncology community since its commercial introduction in 2014.…”