Using all our genomes: Blood‐based liquid biopsies for the early detection of cancer

Abstract

The pursuit of highly sensitive and specific cancer diagnostics based on cell‐free nucleic acids isolated from minimally invasive liquid biopsies has been an area of intense research and commercial effort for at least two decades. Most of these tests detect cancer‐specific mutations or epigenetic modifications on circulating DNA derived from tumor cells (ctDNA). Although recent FDA approvals of both single and multianalyte liquid biopsy companion diagnostic assays are proof of the tremendous progress made in this domain, using ctDNA for the diagnosis of early‐stage (stage I/II) cancers remains challenging due to several factors such as low mutational allele frequency in circulation, overlapping profiles in genomic alterations among diverse cancers, and clonal hematopoiesis. This review discusses these analytical challenges, interim solutions, and the opportunity to complement ctDNA diagnostics with microbiome‐aware analyses that may mitigate several existing ctDNA assay limitations.

Construction of Exosome SORL1 Detection Platform Based on 3D Porous Microfluidic Chip and its Application in Early Diagnosis of Colorectal Cancer

“…[ 15 ] Under the protection of a phospholipid bilayer membrane, [ 16 ] exosomes derived from tumor cells can be detected stably in a variety of body fluids, reflecting the real‐time tumor loading status, and were considered promising tools for liquid biopsy. [ 17,18 ] It is reported that Glypican 1‐positive exosomes can accurately distinguish early pancreatic cancer from benign pancreatic diseases, with a diagnostic sensitivity and specificity reaching 100%; these findings opened a new avenue in the application of exosomes for the early diagnosis of tumors. [ 19,20 ] Simultaneously, the commonly used exosome isolation and detection methods, such as ultracentrifugation and western blot, still rely on large and expensive equipment and are time‐consuming.…”

A nomogram based on metabolic profiling to discriminate lung cancer among patients with lung nodules

“…Liquid biopsy not only plays an important role in tumor diagnosis but also in assessing tumor prognosis, monitoring treatment efficacy and resistance, and treatment selection. 26 Additionally, there are many commercial kits that are currently in use. 26 Metabolic reprogramming is considered one of the hallmarks of cancer.…”

“… 26 Additionally, there are many commercial kits that are currently in use. 26 Metabolic reprogramming is considered one of the hallmarks of cancer. 7 In recent years, metabolic fingerprints have been used as early diagnostic markers of tumors, including for lung adenocarcinoma, 27 colorectal cancer, 28 breast cancer, 29 and early-stage gastric cancer.…”

“…Various models for cancer management that use metabolic fingerprinting have also shown excellent diagnostic efficacy. [26][27][28][29][30][31] It is believed that the advancement of analytical techniques will also increase screening for early-stage cancers.…”

Integrative Serum Metabolic Fingerprints Based Multi‐Modal Platforms for Lung Adenocarcinoma Early Detection and Pulmonary Nodule Classification

“…Still, CTCs show limited sensitivity of 70% and require hours for antibody recognition and enrichment, making it infeasible for large‐scale cancer screening. [ 6 ] At the molecular level, omics tools, including genomics, [ 7 ] proteomics, [ 8 ] and metabolomics, [ 9 ] inform clinical decision‐making for cancer diagnosis and guide precision medicine. Notably, metabolic analysis, which is closer to disease phenotypes, measures the end products of biological activities and represents a promising tool for the detection of early‐stage cancer.…”