Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA As Liquid Biopsy
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
When Cancer Spreads to the Bone
When Cancer Spreads to the Bone John U. (pictured) was diagnosed with kidney cancer which metastasized to the bone over 10 years ago. Since then, he has had over a dozen procedures to stabilize his bones. Cancer occurs when cells in your body their cancer has spread to their bones. start growing and dividing faster than is booklet explains: normal. At rst, these cells may form into • Why bone metastases occur small clumps or tumors. But they can • How they are treated also spread to other parts of the body. When cancer spreads, it is said to have • What patients with bone metastases can “metastasized.” do to prevent broken bones and fractures It is possible for many types of cancer to spread to the bones. People with cancer can live for years after they have been told What is Bone? BONE ANATOMY Many people don’t spend much time thinking about their bones. But there’s a lot going on Trabecular Bone inside them. Bone is living, growing tissue, Blood vessels in bone marrow made up of proteins and minerals. Your bones have two layers. The outer layer— called cortical bone— is very thick. The inner layer—the trabecular (truh-BEH-kyoo-ler) bone—is very spongy. Inside the spongy bone is your bone marrow. It contains stem cells that can develop into white blood cells, red blood cells, and platelets. Cortical Bone The cells that make up the bones are always changing. There are three types of cells that are found only in bone: Osteoclasts (OS-tee-oh-klast), which break down the bone LLC, US Govt. -
Circulating Tumor DNA As Biomarkers for Cancer Detection
Genomics Proteomics Bioinformatics 15 (2017) 59–72 HOSTED BY Genomics Proteomics Bioinformatics www.elsevier.com/locate/gpb www.sciencedirect.com REVIEW Circulating Tumor DNA as Biomarkers for Cancer Detection Xiao Han 1,2,a, Junyun Wang 1,b, Yingli Sun 1,*,c 1 CAS Key Laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China 2 University of Chinese Academy of Sciences, Beijing 100049, China Received 1 July 2016; revised 13 December 2016; accepted 20 December 2016 Available online 7 April 2017 Handled by Cesar Wong KEYWORDS Abstract Detection of circulating tumor DNAs (ctDNAs) in cancer patients is an important com- Precision medicine; ponent of cancer precision medicine ctDNAs. Compared to the traditional physical and biochemical Liquid biopsy; methods, blood-based ctDNA detection offers a non-invasive and easily accessible way for cancer Circulating tumor DNA; diagnosis, prognostic determination, and guidance for treatment. While studies on this topic are Biomarker; currently underway, clinical translation of ctDNA detection in various types of cancers has been Clinical diagnosis; attracting much attention, due to the great potential of ctDNA as blood-based biomarkers for early Cell-free nucleic acids diagnosis and treatment of cancers. ctDNAs are detected and tracked primarily based on tumor- related genetic and epigenetic alterations. In this article, we reviewed the available studies on ctDNA detection and described the representative methods. We also discussed the current understanding of ctDNAs in cancer patients and their availability as potential biomarkers for clin- ical purposes. Considering the progress made and challenges involved in accurate detection of speci- fic cell-free nucleic acids, ctDNAs hold promise to serve as biomarkers for cancer patients, and further validation is needed prior to their broad clinical use. -
Circulating Tumor Cell As a Diagnostic Marker in Primary Lung Cancer
Published OnlineFirst November 3, 2009; DOI: 10.1158/1078-0432.CCR-09-1095 Published Online First on November 3, 2009 as 10.1158/1078-0432.CCR-09-1095 Imaging, Diagnosis, Prognosis Circulating Tumor Cell as a Diagnostic Marker in Primary Lung Cancer Fumihiro Tanaka,1 Kazue Yoneda,1 Nobuyuki Kondo,1 Masaki Hashimoto,1 Teruhisa Takuwa,1 Seiji Matsumoto,1 Yoshitomo Okumura,1 Shakibur Rahman,1 Noriaki Tsubota,2 Tohru Tsujimura,3 Kozo Kuribayashi,4 Kazuya Fukuoka,4 Takashi Nakano,4 and Seiki Hasegawa1 Abstract Purpose: To investigate the diagnostic performance of circulating tumor cells (CTC) in discrimination between primary lung cancer and nonmalignant diseases as well as in prediction of distant metastasis. Patients and Methods: We prospectively evaluated CTCs in 7.5-mL samples of periph- eral blood sampled from patients with a suspicion or a diagnosis of primary lung can- cer. A semiautomated system was used to capture CTCs with an antibody against epithelial cell adhesion molecule. Results: Of 150 eligible patients, 25 were finally diagnosed as having nonmalignant dis- ease, and 125 were diagnosed as having primary lung cancer with (n = 31) or without (n = 94) distant metastasis. CTCs were detected in 30.6% of lung cancer patients and in 12.0% of nonmalignant patients. CTC count was significantly higher in lung cancer pa- tients than in nonmalignant patients, but a receiver operating characteristic (ROC) curve analysis showed an insufficient capability of the CTC test in discrimination be- tween lung cancer and nonmalignant diseases with an area under ROC curve of 0.598 (95% confidence interval, 0.488-0.708; P = 0.122). -
797 Circulating Tumor DNA and Circulating Tumor Cells for Cancer
Medical Policy Circulating Tumor DNA and Circulating Tumor Cells for Cancer Management (Liquid Biopsy) Table of Contents • Policy: Commercial • Coding Information • Information Pertaining to All Policies • Policy: Medicare • Description • References • Authorization Information • Policy History • Endnotes Policy Number: 797 BCBSA Reference Number: 2.04.141 Related Policies Biomarkers for the Diagnosis and Cancer Risk Assessment of Prostate Cancer, #336 Policy1 Commercial Members: Managed Care (HMO and POS), PPO, and Indemnity Plasma-based comprehensive somatic genomic profiling testing (CGP) using Guardant360® for patients with Stage IIIB/IV non-small cell lung cancer (NSCLC) is considered MEDICALLY NECESSARY when the following criteria have been met: Diagnosis: • When tissue-based CGP is infeasible (i.e., quantity not sufficient for tissue-based CGP or invasive biopsy is medically contraindicated), AND • When prior results for ALL of the following tests are not available: o EGFR single nucleotide variants (SNVs) and insertions and deletions (indels) o ALK and ROS1 rearrangements o PDL1 expression. Progression: • Patients progressing on or after chemotherapy or immunotherapy who have never been tested for EGFR SNVs and indels, and ALK and ROS1 rearrangements, and for whom tissue-based CGP is infeasible (i.e., quantity not sufficient for tissue-based CGP), OR • For patients progressing on EGFR tyrosine kinase inhibitors (TKIs). If no genetic alteration is detected by Guardant360®, or if circulating tumor DNA (ctDNA) is insufficient/not detected, tissue-based genotyping should be considered. Other plasma-based CGP tests are considered INVESTIGATIONAL. CGP and the use of circulating tumor DNA is considered INVESTIGATIONAL for all other indications. 1 The use of circulating tumor cells is considered INVESTIGATIONAL for all indications. -
ASTRO Bone Metastases Guideline-Full Version
1 Palliative Radiotherapy for Bone Metastases: An ASTRO Evidence-Based Guideline Stephen T. Lutz, M.D.,* Lawrence B. Berk, M.D., Ph.D.,† Eric L. Chang, M.D.,‡ Edward Chow, M.B.B.S.,§ Carol A. Hahn, M.D.,║ Peter J. Hoskin, M.D.,¶ David D. Howell, M.D.,# Andre A. Konski, M.D.,** Lisa A. Kachnic, M.D.,†† Simon S. Lo, M.B. ChB,§§ Arjun Sahgal, M.D.,║║ Larry N. Silverman, M.D.,¶¶ Charles von Gunten, M.D., Ph.D., FACP,## Ehud Mendel, M.D., FACS,*** Andrew D. Vassil, M.D.,††† Deborah Watkins Bruner, R.N., Ph.D.,‡‡‡ and William F. Hartsell, M.D.§§§ * Department of Radiation Oncology, Blanchard Valley Regional Cancer Center, Findlay, Ohio; † Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida; ‡ Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; § Department of Radiation Oncology, Sunnybrook Odette Cancer Center, University of Toronto, Toronto, Ontario, Canada; ║ Department of Radiation Oncology, Duke University, Durham, North Carolina; ¶ Mount Vernon Centre for Cancer Treatment, Middlesex, UK; # Department of Radiation Oncology, University of Michigan, Mt. Pleasant, Michigan; ** Department of Radiation Oncology, Wayne State University, Detroit, Michigan; †† Department of Radiation Oncology, Boston Medical Center, Boston, Massachusetts; §§ Department of Radiation Oncology, Ohio State University, Columbus, Ohio; ║║ Department of Radiation Oncology, Sunnybrook Odette Cancer Center and the Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada; ¶¶ 21st Century Oncology, Sarasota, Florida; ## The Institute for Palliative Medicine, San Diego Hospice, San Diego, California; *** Neurological Surgery, Ohio State University, Columbus, Ohio; ††† Department of Radiation Oncology, The Cleveland Clinic 2 Foundation, Cleveland, Ohio; ‡‡‡ School of Nursing, University of Pennsylvania, Philadelphia, Pennsylvania; §§§ Department of Radiation Oncology, Good Samaritan Cancer Center, Downers Grove, Illinois Reprint requests to: Stephen Lutz, M.D., 15990 Medical Drive South, Findlay, OH 45840. -
Review of Intra-Arterial Therapies for Colorectal Cancer Liver Metastasis
cancers Review Review of Intra-Arterial Therapies for Colorectal Cancer Liver Metastasis Justin Kwan * and Uei Pua Department of Vascular and Interventional Radiology, Tan Tock Seng Hospital, Singapore 388403, Singapore; [email protected] * Correspondence: [email protected] Simple Summary: Colorectal cancer liver metastasis occurs in more than 50% of patients with colorectal cancer and is thought to be the most common cause of death from this cancer. The mainstay of treatment for inoperable liver metastasis has been combination systemic chemotherapy with or without the addition of biological targeted therapy with a goal for disease downstaging, for potential curative resection, or more frequently, for disease control. For patients with dominant liver metastatic disease or limited extrahepatic disease, liver-directed intra-arterial therapies including hepatic arterial chemotherapy infusion, chemoembolization and radioembolization are alternative treatment strategies that have shown promising results, most commonly in the salvage setting in patients with chemo-refractory disease. In recent years, their role in the first-line setting in conjunction with concurrent systemic chemotherapy has also been explored. This review aims to provide an update on the current evidence regarding liver-directed intra-arterial treatment strategies and to discuss potential trends for the future. Abstract: The liver is frequently the most common site of metastasis in patients with colorectal cancer, occurring in more than 50% of patients. While surgical resection remains the only potential Citation: Kwan, J.; Pua, U. Review of curative option, it is only eligible in 15–20% of patients at presentation. In the past two decades, Intra-Arterial Therapies for Colorectal major advances in modern chemotherapy and personalized biological agents have improved overall Cancer Liver Metastasis. -
The Interplay of Circulating Tumor DNA and Chromatin Modification
Zhang et al. Molecular Cancer (2019) 18:36 https://doi.org/10.1186/s12943-019-0989-z REVIEW Open Access The interplay of circulating tumor DNA and chromatin modification, therapeutic resistance, and metastasis Lei Zhang1,2,3†, Yiyi Liang1,2,3†, Shifu Li1,2,3†, Fanyuan Zeng1,2,3†, Yongan Meng1,2,3†, Ziwei Chen1,2,3, Shuang Liu3, Yongguang Tao1,2,3,4* and Fenglei Yu4* Abstract Peripheral circulating free DNA (cfDNA) is DNA that is detected in plasma or serum fluid with a cell-free status. For cancer patients, cfDNA not only originates from apoptotic cells but also from necrotic tumor cells and disseminated tumor cells that have escaped into the blood during epithelial-mesenchymal transition. Additionally, cfDNA derived from tumors, also known as circulating tumor DNA (ctDNA), carries tumor-associated genetic and epigenetic changes in cancer patients, which makes ctDNA a potential biomarker for the early diagnosis of tumors, monitory and therapeutic evaluations, and prognostic assessments, among others, for various kinds of cancer. Moreover, analyses of cfDNA chromatin modifications can reflect the heterogeneity of tumors and have potential for predicting tumor drug resistance. Keywords: ctDNA, Chromatin modification, Therapeutic resistance, Metastasis, Tumor heterogeneity Biological features of ctDNA enter the blood in single, double or triple forms, and Peripheral circulating free DNA is DNA that is detected thus most ctDNA shows significant fragmentary charac- in plasma or serum fluid with a cell-free status. It may teristics. Moreover, the half-life of ctDNA in the blood originate from apoptosis or necrosis. The amount of cir- circulation is less than 2 hours [3]. -
Circulating Cell-Free DNA in Hepatocellular Carcinoma: Current Insights and Outlook
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by edoc REVIEW published: 26 March 2018 doi: 10.3389/fmed.2018.00078 Circulating Cell-Free DNA in Hepatocellular Carcinoma: Current Insights and Outlook Charlotte K. Y. Ng1,2*, Giovan Giuseppe Di Costanzo3, Luigi M. Terracciano1 and Salvatore Piscuoglio1* 1 Institute of Pathology, University Hospital Basel, Basel, Switzerland, 2 Department of Biomedicine, Hepatology Laboratory, University of Basel, Basel, Switzerland, 3 Department of Transplantation – Liver Unit, Cardarelli Hospital, Naples, Italy Over the past decade, the advancements in massively parallel sequencing have pro- vided a new paradigm in biomedical research to uncover the genetic basis of human diseases. Integration of ‘omics information has begun transforming clinical management of cancer patients in terms of diagnostics and treatment options, giving rise to the era of precision medicine. Currently, nucleic acids for molecular profiling for patients diagnosed with hepatocellular carcinoma (HCC) are typically obtained from resected tumor mate- rials or transplanted neoplastic liver and occasionally from biopsies. Given the intrinsic risks associated with such invasive procedures, circulating cell-free DNA (cfDNA) has been proposed as an alternative source for tumor DNA. Circulating cfDNA is a type of Edited by: cell-free nucleic acid that derives from apoptotic, necrotic, as well as living eukaryotic Venancio Avancini Alves, University of São Paulo, Brazil cells. Importantly, the detection of abnormal forms of circulating cfDNA that originate Reviewed by: from cancer cells provides a new tool for cancer detection, disease monitoring, and Fernando Schmitt, molecular profiling. Currently, cfDNA is beginning to be adopted into clinical practice Universidade do Porto, Portugal Marco Volante, as a non-invasive tool to monitor disease by tracking the evolution of disease-specific Università degli Studi di Torino, Italy genetic alterations in several major cancer types. -
When Cancer Spreads to the Bone
When Cancer Spreads to the Bone What is bone metastasis? As a cancerous tumor grows, cancer cells may break away and be carried to other parts of the body by the blood or lymphatic system. This is called metastasis. It is called metastases when there are multiple areas in the bone with cancer. One of the most common places cancer spreads to is the bones, especially cancers of the breast, prostate, kidney, thyroid, and lung. When a new tumor develops in the bones as a result of metastasis, it is not called bone cancer. Instead, it is named after the area in the body where the cancer started. For example, lung cancer that spreads to the bones is called metastatic lung cancer. What are the symptoms of bone metastasis? When cancer spreads to the bones, the bones can become weak or fragile. Bones most commonly affected include the upper leg bones, the upper arm bones, the spine, the ribs, the pelvis, and the skull. Bone pain is the most common symptom. Bone breaks, called fractures, may also occur. Bones damaged by cancer may ONCOLOGY. CLINICAL SOCIETY AMERICAN OF 2004 © LLC. EXPLANATIONS, MORREALE/VISUAL ROBERT BY ILLUSTRATION also release high levels of calcium into the blood, called hypercalcemia, which may be detected in your blood work. If the cancer is advanced, this can cause nausea, fatigue, thirst, frequent urination, and confusion. If a tumor presses on the spinal cord, a person may feel weakness or numbness in the legs, arms, or abdomen, or develop constipation or the inability to control urination. -
Highly Sensitive Detection of Sentinel Lymph Node Metastasis of Breast Cancer by Digital PCR for RASSF1A Methylation
2382 ONCOLOGY REPORTS 42: 2382-2389, 2019 Highly sensitive detection of sentinel lymph node metastasis of breast cancer by digital PCR for RASSF1A methylation MIZUHO ABE, NAOFUMI KAGARA, TOMOHIRO MIYAKE, TOMONORI TANEI, YASUTO NAOI, MASAFUMI SHIMODA, KENZO SHIMAZU, SEUNG JIN KIM and SHINZABURO NOGUCHI Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565‑0871, Japan Received June 4, 2019; Accepted September 19, 2019 DOI: 10.3892/or.2019.7363 Abstract. One-step nucleic acid amplification (OSNA) and is confirmed by postoperative pathological examination of targeting cytokeratin 19 (CK19) mRNA expression and permanent sections (3,4). One‑step nucleic acid amplification pathological examination are widely used for the intraop- (OSNA) can be used to detect SN metastasis through the erative diagnosis of sentinel node (SN) metastasis. The aim amplification of cytokeratin 19 (CK19) mRNA (which is of the present study was to develop a novel assay for detecting expressed in tumor cells, but not normal cells of LNs) with the SN metastasis by targeting Ras association domain-containing same accuracy as routine pathological examination (5). OSNA protein 1 (RASSF1A) methylation in tumor cells, and to is also used to determine total tumor load (TTL) in SNs as the compare its performance with OSNA. Using digital PCR with sum of CK19 mRNA copies, which is reportedly useful for methylation-specific restriction enzymes (RE-dMSP), our predicting non-SN metastatic status (6,7), as well as patient assay was able to detect ≥3 copies of methylated DNA per prognosis (8). well, and was ≥10 times more sensitive than real‑time PCR However, TTL determination by OSNA does not always with bisulfite modification. -
Circulating Tumor Cells
The ability to isolate and molecularly analyze circulating tumor cells is becoming a reality. The Closest Exit May Be Behind You. Photograph courtesy of Craig Damlo. www.soapboxrocket.com. Circulating Tumor Cells: A Window Into Tumor Development and Therapeutic Effectiveness Gisela Cáceres, PhD, John A. Puskas, PhD, and Anthony M. Magliocco, MD Background: Circulating tumor cells (CTCs) are an important diagnostic tool for understanding the meta- static process and the development of cancer. Methods: This review covers the background, relevance, and potential limitations of CTCs as a measurement of cancer progression and how information derived from CTCs may affect treatment efficacy. It also highlights the difficulties of characterizing these rare cells due to the limited cell surface molecules unique to CTCs and each particular type of cancer. Results: The analysis of cancer in real time, through the measure of the number of CTCs in a “liquid” biopsy specimen, gives us the ability to monitor the therapeutic efficacy of treatments and possibly the metastatic potential of a tumor. Conclusions: Through novel and innovative techniques yielding encouraging results, including microfluidic techniques, isolating and molecularly analyzing CTCs are becoming a reality. CTCs hold promise for under- standing how tumors work and potentially aiding in their demise. Introduction States is attributed to cancer.2 The search for biomark- Cancer is a comprehensive term that includes a group ers that allow early detection and may therefore affect of diseases characterized by host cells growing with- the outcome of the disease is critical. The ability of out control. It has a multifactorial origin and, even cancer cells to spread in the body, producing metas- though many cancers are directly associated with risk tasis, is one of the most relevant characteristics of the factors in modern life, cancer is an ancient disease, disease and the cause of most cancer deaths. -
Circulating Tumor DNA Testing Opens New Perspectives in Melanoma Management
cancers Review Circulating Tumor DNA Testing Opens New Perspectives in Melanoma Management 1, 1, 1 1 Alessandra Sacco y , Laura Forgione y, Marianeve Carotenuto , Antonella De Luca , Paolo A. Ascierto 2 , Gerardo Botti 3 and Nicola Normanno 1,* 1 Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Naples, Italy; [email protected] (A.S.); [email protected] (L.F.); [email protected] (M.C.); [email protected] (A.D.L.) 2 Department of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione Pascale, 80131 Napoli, Italy; [email protected] 3 Scientific Direction, Istituto Nazionale Tumori IRCCS Fondazione Pascale, 80131 Napoli, Italy; [email protected] * Correspondence: [email protected]; Tel.: +39-081-5903-826 These authors contributed equally to this work. y Received: 15 September 2020; Accepted: 8 October 2020; Published: 10 October 2020 Simple Summary: Melanoma, like other solid tumors, releases DNA molecules that are referred to as circulating tumor DNA (ctDNA), into the blood and other biological fluids. ctDNA analysis performed with molecular biology techniques can provide important information on the aggressiveness of the disease and its genetic characteristics. This review aims to highlight all the possible clinical applications of ctDNA analysis that can contribute to an improvement in the diagnosis and therapy of melanoma. Abstract: Malignant melanoma accounts for about 1% of all skin cancers, but it causes most of the skin cancer-related deaths. Circulating tumor DNA (ctDNA) testing is emerging as a relevant tool for the diagnosis and monitoring of cancer.