{"doi":"10.1111/cts.12776","title":"Liquid Biopsy: Emergence of an Alternative Cancer Detection Method","abstract":"Traditional biopsy consists of the removal of cancerous or suspected cancerous tissue for diagnosis (i.e., needle biopsy, bone or marrow biopsy, etc.). Liquid biopsy has recently been presented as an alternative for earlier detection and to help inform clinical decision making. In this commentary, we detail the translational path that liquid biopsy followed to move from concept to clinical care, and highlight barriers and facilitators to its successful translation. Biopsies traditionally involve the removal of solid tissue for examination; done via needle biopsy, computed tomography-guided biopsy, bone marrow biopsy, or surgical biopsy. These procedures come with inherent risks to the patient, such as infection and complications due to tumor location, as well as diagnostic risks, such as insufficient material or sampling bias due to tumor heterogeneity.1 Liquid biopsy is the removal of blood or other bodily fluid to detect cancerous cells or cancerous DNA that arises from malignant or nonmalignant cells in the body. Compared with traditional biopsy, liquid biopsy is less invasive, offers reduced risks of complication, increased ability for longitudinal monitoring, and the possibility of quickly identifying clonal evolution and the development of resistances in cancer cells.2 The presence of cell-free DNA (cfDNA) in human blood was first noted by a pair of French physicians, Mandel and Métais, in 1948 (Figure 1).3 In 1977, the discovery of elevated levels of cfDNA in patients with cancer was made, opening the door for further explorations into the connection between the two.4 Primary tumor cells undergo apoptosis, necrosis, phagocytosis, or cell detachment and, thus, release tumor-derived cfDNA, otherwise known as circulating tumor DNA (ctDNA), into the bloodstream. As genetic sequencing technology improved with the advent of polymerase chain reaction and eventually next generation sequencing technologies, ctDNA was more thoroughly characterized.5 Catalyzed by the new sequencing technologies, explorations into blood samples from the cancer patient populations yielded known cancer-related mutations in the ctDNA of both patients with solid and liquid tumors, lending credence to the hypothesis that the genetic material of cancerous cells could be monitored in blood.6 Following the discovery of increased levels of cfDNA in patients with cancer, liquid biopsies have been explored as a potentially safer, more effective clinical detection method. Early detection of ctDNA via a simple blood draw offers the potential for population-level screening, early detection, intervention, and progressive monitoring throughout treatment; in short, it has potential utility across the cancer care continuum.2 Liquid biopsy’s low cost, minimal collection risks, and potential for serial or repeated testing make it an attractive alternative to traditional biopsies. Roche Diagnostic’s Cobas EGFR Mutation Test version 2 is currently the only US Food and Drug Administration (FDA) approved liquid biopsy, and, thus, serves as a case study for the successful translation of this technology. The test is an adaptation of an existing tissue biopsy system for identifying specific actionable mutations in non-small cell lung cancer (NSCLC). The tissue version of the Cobas system received premarket approval from the FDA in 2013, and full approval in 2015. Cobas was approved as a diagnostic tool for identifying patients with NSCLC with specific mutations in the EGFR gene for whom EGFR inhibitors (gefitinib and erlotinib) may be particularly effective. This approval was based on almost a decade of both laboratory and clinical research proving the effectiveness of inhibitor treatment in both primary NSCLC cell lines and patients with specific EGFR mutations.7 The liquid Cobas test, also known as Cobas EGFR Mutation Test version 2, applies the concepts and technology from the original tissue test (Cobas version 1) with an additional innovation that allows for extraction ","journal":"Clinical and Translational Science","year":2020,"id":84498,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9515,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":274116,"name":"Megan L. Settell","orcid":"0000-0002-2924-360X","position":1,"is_corresponding":false},{"id":306789,"name":"Shaheen Kurani","orcid":"0000-0003-2366-7505","position":2,"is_corresponding":false},{"id":434799,"name":"Elizabeth C. Eckert","orcid":null,"position":3,"is_corresponding":false},{"id":242419,"name":"Minetta C. Liu","orcid":"0000-0002-8206-5232","position":4,"is_corresponding":false},{"id":371974,"name":"Alexandra J. Greenberg","orcid":"0000-0001-5935-3239","position":5,"is_corresponding":false},{"id":434798,"name":"Ethan Law","orcid":null,"position":0,"is_corresponding":true}],"reference_count":11,"raw_metadata":null,"created_at":"2026-07-18T21:55:38.506333Z","pmid":"32233063","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}