Abstract IA09: The promise of liquid biopsy in the early detection of cancer: Hope or hype?

Abstract

Abstract Noninvasive technologies and methodologies are urgently needed for a population-based early detection and screening. Liquid biopsy continues to draw the attention of patients and physicians alike. Liquid biopsies have the potential to help clinicians screen for disease, stratify patients to the best treatment, and monitor treatment response and resistance mechanisms in the tumor. A liquid biopsy can be used for molecular characterization of the tumor, and its noninvasive nature allows repeat sampling to monitor genetic changes over time without the need for a tissue biopsy. Liquid biopsy generally refers to measuring molecular changes, e.g., genomic, proteomic, metabolomics, epigenetic, and other “omics”-derived changes, in circulating tumor cells (CTCs), cell-free DNA (cfDNA), and exosomes. However, the real success of liquid biopsy continues to evade us. There are several challenges in detecting tumor-derived mutations in plasma or in other body fluids. This is partly due to the fact that the amount of circulating DNA usually is very low. Recent technological developments and the analytics being applied to liquid biopsies are now capable of reproducibly detecting mutations at very low allelic frequencies. Advances have also been made in droplet digital PCR (ddPCR), next-generation sequencing (NGS), beads, emulsion, amplification and magnetics (BEAMing), and amplification of refractory mutation system (ARMS), to name but a few. Ultimately, the choice of platforms and required detection limit will depend on the clinical sample being analyzed, as the most sensitive methods are reported to detect allelic frequencies of as little as 0.01%; if achieved in a liquid biopsy setting, this level of detection would be sufficient to gain knowledge of a tumor genotype and rule out the need for a tissue biopsy. Despite these challenges, the advantage of liquid biopsies over other traditional tissue-based methodologies is very promising, including the ability for longitudinal monitoring, which could help clinical oncologists gain a broader molecular understanding of the disease. Additionally, liquid biopsy could also facilitate cancer progression and treatment monitoring in follow-up visits. Cancer detection in liquid biopsy achieves repetitive sampling that is limited in histologic examination, and it provides a more economical and practical noninvasive detection compared to radiation-based imaging methods such as computed tomography. Furthermore, liquid biopsy may also shed light on tumor heterogeneity and may provide a more comprehensive picture of the genetic and proteomic alternations of the tumor. The National Cancer Institute is supporting a number of programs that are addressing some of the challenges described above and pursuing careful selection of candidate markers (mutations, epigenomic changes, proteomic alterations, etc.), developing better analytical methods and sensitive molecular technologies that may contribute to early cancer detection and monitoring. The speaker will describe the objectives of these programs and provide updates. Citation Format: Sudhir Srivastava. The promise of liquid biopsy in the early detection of cancer: Hope or hype? [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr IA09.