Distant metastases harbor unique genomic characteristics not detectable in the corresponding primary tumor of the same patient and metastases located at different sites show a considerable ...intrapatient heterogeneity. Thus, the mere analysis of the resected primary tumor alone (current standard practice in oncology) or, if possible, even reevaluation of tumor characteristics based on the biopsy of the most accessible metastasis may not reveal sufficient information for treatment decisions. Here, we propose that this dilemma can be solved by a new diagnostic concept: liquid biopsy, that is, analysis of therapeutic targets and drug resistance-conferring gene mutations on circulating tumor cells (CTC) and cell-free circulating tumor DNA (ctDNA) released into the peripheral blood from metastatic deposits. We discuss the current challenges and future perspectives of CTCs and ctDNA as biomarkers in clinical oncology. Both CTCs and ctDNA are interesting complementary technologies that can be used in parallel in future trials assessing new drugs or drug combinations. We postulate that the liquid biopsy concept will contribute to a better understanding and clinical management of drug resistance in patients with cancer.
Different technologies, such as quantitative real-time PCR or microarrays, have been developed to measure microRNA (miRNA) expression levels. Quantification of miRNA transcripts implicates data ...normalization using endogenous and exogenous reference genes for data correction. However, there is no consensus about an optimal normalization strategy. The choice of a reference gene remains problematic and can have a serious impact on the actual available transcript levels and, consequently, on the biological interpretation of data.
In this review article we discuss the reliability of the use of small RNAs, commonly reported in the literature as miRNA expression normalizers, and compare different strategies used for data normalization.
A workflow strategy is proposed for normalization of miRNA expression data in an attempt to provide a basis for the establishment of a global standard procedure that will allow comparison across studies.
As the release of tumor-associated DNA into blood circulation is a common event in patients with cancer, screening of plasma or serum DNA may provide information on genetic and epigenetic profiles ...associated with breast cancer development, progression, and response to therapy. Quantitative testing of circulating DNA can reflect tumor burden, and molecular characterization of circulating DNA can reveal important tumor characteristics relevant to the choice of targeted therapies in individual patients. Contrary to circulating DNA from blood that presents molecular changes in tumor DNA in real time, tissue biopsies can deliver only a spatially and temporally limited snapshot of the heterogeneous tumor. Analyses of circulating DNA might provide prognostic and predictive information and therefore advance personalized medicine. However, standardization of different technical platforms as well as the control of pre-analytical and analytical factors is mandatory before its introduction into clinical practice. In the present review, we discussed technical aspects and clinical relevance of the analyses of circulating plasma/serum DNA in patients with breast cancer.
Liquid biopsies: Potential and challenges Heidrich, Isabel; Ačkar, Lucija; Mossahebi Mohammadi, Parinaz ...
International journal of cancer,
1 February 2021, Letnik:
148, Številka:
3
Journal Article
Recenzirano
Odprti dostop
The analysis of tumor cells or tumor cell products obtained from blood or other body fluids (“liquid biopsy” LB) provides a broad range of opportunities in the field of oncology. Clinical application ...areas include early detection of cancer or tumor recurrence, individual risk assessment and therapy monitoring. LB allows to portray the entire disease as tumor cells or tumor cell products are released from all metastatic or primary tumor sites, providing comprehensive and real‐time information on tumor cell evolution, therapeutic targets and mechanisms of resistance to therapy. Here, we focus on the most prominent LB markers, circulating tumor cells (CTCs) and circulating tumor‐derived DNA (ctDNA), in the blood of patients with breast, prostate, lung and colorectal cancer, as the four most frequent tumor types in Europe. After a brief introduction of key technologies used to detect CTCs and ctDNA, we discuss recent clinical studies on these biomarkers for early detection and prognostication of cancer as well as prediction and monitoring of cancer therapies. We also point out current methodological and biological limitations that still hamper the implementation of LB into clinical practice.
Progress in sensitive analytical approaches has opened new avenues for the detection of cells or products such as circulating cell-free DNA released by tumors. These 'liquid biopsies' are being ...explored in clinical trials for early cancer detection, prediction of recurrent disease, and assessment of therapeutic resistance mechanisms.
Hematogeneous tumor cell dissemination is a key step in cancer progression. The detection of CTCs in the peripheral blood of patients with solid epithelial tumors (e.g., breast, prostate, lung and ...colon cancer) holds great promise, and many exciting technologies have been developed over the past years. However, the detection and molecular characterization of circulating tumor cells (CTCs) remain technically challenging. The identification and characterization of CTCs require extremely sensitive and specific analytical methods, which are usually a combination of complex enrichment and detection procedures. CTCs occur at very low concentrations of one tumor cell in the background of millions of normal blood cells and the epithelial-mesenchymal plasticity of CTCs can hamper their detection by the epithelial markers used in current CTC assays. In the present review, we summarize current methods for the enrichment and detection of CTCs and discuss the key challenges and perspectives of CTC analyses within the context of improved clinical management of cancer patients.
Prostate cancer represents the most common non-skin cancer type in men. Unmet needs include understanding prognosis to determine when intervention is needed and what type, prediction to guide the ...choice of a systemic therapy, and response indicators to determine whether a treatment is working. Over the past decade, the "liquid biopsy," characterized by the analysis of tumor cells and tumor cell products such as cell-free nucleic acids (DNA, microRNA) or extracellular vesicles circulating in the blood of cancer patients, has received considerable attention.
Among those biomarkers, circulating tumor cells (CTCs) have been most intensively analyzed in prostate cancer. Here we discuss recent studies on the enumeration and characterization of CTCs in peripheral blood and how this information can be used to develop biomarkers for each of these clinical contexts. We focus on clinical applications in men with metastatic castration-resistant prostate cancer, in whom CTCs are more often detected and at higher numbers, and clinical validation for different contexts of use is most mature.
The overall goal of CTC-based liquid biopsy testing is to better inform medical decision-making so that patient outcomes are improved.
Real-time monitoring of changes in cells or cell products released from malignant lesions into the blood has opened new diagnostic avenues (“liquid biopsy”). In this issue of Cancer Cell, Best and ...colleagues describe that tumor-associated blood platelets provide specific information on the location and molecular composition of the primary tumor.
Real-time monitoring of changes in cells or cell products released from malignant lesions into the blood has opened new diagnostic avenues (“liquid biopsy”). In this issue of Cancer Cell, Best and colleagues describe that tumor-associated blood platelets provide specific information on the location and molecular composition of the primary tumor.
Carcinoma cells found in the blood of cancer patients are predictors of metastatic progression and may guide treatment decisions. Most of the current strategies for detecting circulating tumor cells ...(CTC) are based on the epithelial markers epithelial cell adhesion molecule and keratin; however, evidence is accumulating that in certain tumor types, these epithelial markers are downregulated during tumor cell dissemination, hampering the detection of CTCs. This short review discusses the implications of the cellular changes of tumor cells during the metastatic cascade on CTC diagnostics.
Keratins are essential elements of the cytoskeleton of normal and malignant epithelial cells. Because carcinomas commonly maintain their specific keratin expression pattern during malignant ...transformation, keratins are extensively used as tumor markers in cancer diagnosis including the detection of circulating tumor cells in blood of carcinoma patients. Interestingly, recent biological insights demonstrate that epithelial keratins should not only be considered as mere tumor markers. Emerging evidence suggests an active biological role of keratins in tumor cell dissemination and metastasis. In this review, we illustrate the family of keratin proteins, summarize the latest biological insights into keratin function related to cancer metastasis and discuss the current use of keratins for detection of CTCs and other blood biomarkers used in oncology.
PDF
