Pathologists and liquid biopsies: to be or not to be?
- 3.6k Downloads
Recently, the advent of therapies targeting genomic alterations has improved the care of patients with certain types of cancer. While molecular targets were initially detected in nucleic acid samples extracted from tumor tissue, detection of nucleic acids in circulating blood has allowed the development of what has become known as liquid biopsies, which provide a complementary and alternative sample source allowing identification of genomic alterations that might be addressed by targeted therapy. Consequently, liquid biopsies might rapidly revolutionize oncology practice in allowing administration of more effective treatments. Liquid biopsies also provide an approach towards short-term monitoring of metastatic cancer patients to evaluate efficacy of treatment and/or early detection of secondary mutations responsible for resistance to treatment. In this context, pathologists, who have already been required in recent years to take interest in the domain of molecular pathology of cancer, now face new challenges. The attitude of pathologists to and level of involvement in the practice of liquid biopsies, including mastering the methods employed in molecular analysis of blood samples, need close attention. Regardless of the level of involvement of pathologists in this new field, it is mandatory that oncologists, biologists, geneticists, and pathologists work together to coordinate the pre-analytical, analytical, and post-analytical phases of molecular assessment of tissue and liquid samples of individual cancer patients. The challenges include (1) implementation of effective and efficient procedures for reception and analysis of liquid and tissue samples for histopathological and molecular evaluation and (2) assuring short turn-around times to facilitate rapid optimization of individual patient treatment. In this paper, we will review the following: (1) recent data concerning the concept of liquid biopsies in oncology and its development for patient care, (2) advantages and limitations of molecular analyses performed on blood samples compared to those performed on tissue samples, and (3) short-term challenges facing pathologists in dealing with liquid biopsies of cancer patients and new strategies to early detect metastatic tumor cell clones.
KeywordsLiquid biopsy Free circulating DNA Circulating tumor cells Personalized medicine Genomic alterations Pathology
Compliance with ethical standards
The authors declare to respect all ethical standards.
Conflict of interest
PH declares receiving honoraria from pharmaceutical (AstraZeneca, Roche, Novartis, Bristol Myers Squibb, MSD) and biotechnology (Qiagen, Janssen, Biocartis) companies for advisory board meetings. HP declares receiving honoraria from pharmaceutical companies for advisory board meeting and also unrestricted grants for research (Bristol Myers Squibb, Eli Lilly, Roche, Boehringer-Ingelheim, Astra Zeneca, Novartis).
- 1.Committee on Policy Issues in the Clinical Development and Use of Biomarkers for Molecularly Targeted Therapies, Board on Health Care Services, Institute of Medicine, The National Academies of Sciences, Engineering, and Medicine; Graig LA, Phillips, JK, Moses, HL, editors. Biomarker tests for molecularly targeted therapies: key to unlocking precision medicine. Washington (DC): National Academies Press (US); 2016.Google Scholar
- 16.Ilie M, Hofman V, Long E, et al. (2014) Current challenges for detection of circulating tumor cells and cell-free circulating nucleic acids, and their characterization in non-small cell lung carcinoma patients. What is the best blood substrate for personalized medicine? Ann Transl Med 2:107. doi: 10.3978/j.issn.2305-5839.2014.08.11 PubMedPubMedCentralGoogle Scholar
- 25.Alix-Panabières C, Bartkowiak K, Pantel K (2016) Functional studies on circulating and disseminated tumor cells in carcinoma patients. Mol OncolGoogle Scholar
- 31.Hofman V, Ilie MI, Long E, et al. (2011) Detection of circulating tumor cells as a prognostic factor in patients undergoing radical surgery for non-small-cell lung carcinoma: comparison of the efficacy of the CellSearch Assay™ and the isolation by size of epithelial tumor cell method. Int J Cancer 129:1651–1660CrossRefPubMedGoogle Scholar
- 35.Morrow CJ, Trapani F, Metcalf RL, et al (2016) Tumourigenic non-small-cell lung cancer mesenchymal circulating tumour cells: a clinical case study. Ann OncolGoogle Scholar
- 60.Schreuer M, Meersseman G, Van Den Herrewegen S, et al. (2016) Quantitative assessment of BRAF V600 mutant circulating cell-free tumor DNA as a tool for therapeutic monitoring in metastatic melanoma patients treated with BRAF/MEK inhibitors. J Transl Med 14:95. doi: 10.1186/s12967-016-0852- CrossRefPubMedPubMedCentralGoogle Scholar
- 84.Ilie M, Hofman V, Long E, et al. (2016) PD-L1 expression in primary tumor and circulating tumor cells in patients with small cell lung carcinomas. AACR, New Orleans abstract N°Google Scholar
- 85.Ilie M, Szafer-Glusman E, Hofman V, et al (2016) PD-L1 expression in primary tumor and circulating tumor cells in patients with advanced non-small cell lung cancer. Virchows Archiv ECP abstract N°. XXI International Congress of the International Academy of Pathology and 28 th Congress of the European Society of Pathology, Cologne, Germany. Thoracic Pathology OFP-13, 003. Virchow Archivs 2016, in pressGoogle Scholar