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The Precision Medicine Approach in Oncology
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
As with other tumor types, blood tests to identify circulating tumor cells (CTCs), or DNA or proteins shed from the tumor, represent the most promising approaches for the future. However, none have been validated or commercialized to date. A blood test to detect CTCs would be useful not just for screening purposes, but also to monitor disease progression and to gauge prognosis and guide treatment decisions. In other cancer types, CTC screening technologies have made significant progress, and usually rely on the detection of biomarkers such as epithelial cell adhesion molecules overexpressed on the surface of tumor cells. Unfortunately, brain tumor cells from aggressive diseases such as glioblastoma multiforme tend to lack these biomarkers, and so other methods of detecting brain tumor CTCs in the blood are required which has delayed progress. One approach being studied is the detection of telomerase activity which is elevated in nearly all tumor cells but not in normal cells. One such study was based on the use of an adenoviral detection system to successfully detect CTCs in patients with brain tumors, although differentiating brain tumor CTCs from those originating from other types of cancers remains problematic. It has been suggested that this approach may be useful to help interpret treatment response in patients receiving radiotherapy, although an assay based on this approach is not yet commercially available.
Biomarkers for the Immune Checkpoint Inhibitors
Published in Sherry X. Yang, Janet E. Dancey, Handbook of Therapeutic Biomarkers in Cancer, 2021
Weijie Ma, Sixi Wei, Eddie C. Tian, Tianhong Li
Traditional blood-based cellular and cytokine assays are inadequate to evaluate treatment responses to immune checkpoint inhibitors. Modern non-invasive blood tests have been or are being optimized to detect circulating tumor cells (CTCs), exosomes, and fragments of tumor nucleic acids (DNA, RNA, or miRNA) as well as immune cells that are shed into the blood from both primary and metastatic tumor sites and lymphoid organs. These blood-based cellular immune biomarkers have shown great promise in predicting response to CBA therapy because of specimen accessibility, opportunity for serial monitoring, quantitative measurement, and the availability of the unique analytic platforms. We summarize the most studied blood biomarkers in this section.
Introduction
Published in Nusrat Rabbee, Biomarker Analysis in Clinical Trials with R, 2020
Biomarkers can be biological properties or molecules that can be detected and measured in parts of the body like the blood or tissue. Biomarkers can be specific cells, molecules, or genes, gene products, enzymes, or hormones. Complex organ functions or general characteristic changes in biological structures can also serve as biomarkers [1]. In early phase clinical trials, the drug manufacturer is focused on developing MoA assays for the drug. There is extensive literature about the development of MoA assays, as well as on developing other PD biomarkers, which measure further downstream molecular, biochemical, and physiological changes. Let us take an example of the latter type of PD biomarkers, specifically blood-based biomarkers. (i) In oncology, in order to study the pharmacologic effect of the drug on cancer tissues, an invasive biopsy of the actual tumor is usually needed. Current progress of science permits us to measure blood-based biomarkers of circulating tumor cells as alternative biomarkers of antitumor activity. (ii) In brain disorders, like Alzheimer’s disease, blood biomarkers are less prevalent, since brain disorders may not have peripheral manifestation. However, blood and cerebrospinal fluid (CSF)-based biomarkers are presently an active area of research and development in neurology. (iii) In cardiovascular disease, hemoglobin A1c may be used as a PD/response biomarker when evaluating patients with diabetes to assess response to antihyperglycemic agents.
Contemporary evidence on colorectal liver metastases ablation: toward a paradigm shift in locoregional treatment
Published in International Journal of Hyperthermia, 2022
Yuan-Mao Lin, Reto Bale, Kristy K. Brock, Bruno C. Odisio
The detection of circulating free tumor DNA, plasma microRNA, and circulating tumor cells, which are encompassed by the term ‘liquid biopsy’, is currently used clinically for therapeutic guidance, especially for the tumors with intratumor heterogeneity and clonal heterogeneity such as colorectal cancers. The technique could supplement existing clinical tools by improving screening, early detection, staging, recurrence identification, and prediction of clinical outcomes after treatment. Serial monitoring of the levels of circulating free tumor DNA during treatments can provide early detection of early disease progression in patients undergoing anti-EGFR therapies and immune-checkpoint inhibitors [133–136]. Similarly, the circulating tumor cells might represent a predictive biomarker of early response to chemotherapy and targeted agents [137,138], which might guide escalation or de-escalation of systemic treatment. Also, a challenge in CLM treatment is the development of resistance to systemic treatment, and ablation has been linked in some animal studies with aggressive tumor biological changes and tumor growth promotion [139,140]. It has been reported that liquid biopsy can detect oncogenic mutations in plasma before radiologic progression [141,142]. The liquid biopsy may provide serial monitoring of tumor heterogeneity and evolution over time and guiding clinical decisions [143]. Despite its intriguing potential, the clinical practice of liquid biopsy on patients undergoing ablation is limited due to the lack of standardization of the test and clear demonstration of its clinical benefits to date.
The concept revolution of gut barrier: from epithelium to endothelium
Published in International Reviews of Immunology, 2021
Song Liu, Peng Song, Feng Sun, Shichao Ai, Qiongyuan Hu, Wenxian Guan, Meng Wang
The importance of endothelial barrier in the prevention of cancer metastasis has been reported recently. Circulating tumor cells (CTCs) can be frequently observed in patients with malignancies, however not all of them eventually develop metastasis. In fact, tumor cells that invade into circulatory system become CTCs and can be detected by advanced cell technology. After surviving from shear stress and circulatory immune cells, CTCs can attach to vascular ECs. The interaction between them determines the fate of CTCs, i.e., whether or not they could escape from the vascular endothelial barrier and extravasate into surrounding tissues, where they will form micrometastasis and potentially develop into detectable metastatic sites in the new environment. The interaction between vascular ECs and CTCs is regulated by sophisticated mechanism that involves signaling pathways, ligand-receptor molecules and circulating immune cells. Especially, CTCs are capable to produce certain cytokines and chemokines, which will increase the permeability of vasculature and thereby contributing to the extravasation of themselves [23–25]. The pathogenesis of intravasation and extravasation of endothelial barrier by cancer cells and its significance in the development of metastasis have been well reviewed elsewhere [26].
Proteogenomic examination of esophageal squamous cell carcinoma (ESCC): new lines of inquiry
Published in Expert Review of Proteomics, 2020
Shobha Dagamajalu, Manavalan Vijayakumar, Rohan Shetty, D. A. B. Rex, Chinmaya Narayana Kotimoole, T. S. Keshava Prasad
The detection and isolation of circulating tumor cells are being used for monitoring disease progression and recurrence in various cancers [87]. Bobek et al. have successfully cultured CTCs of esophageal cancer and suggested this could help in the future to decide the treatment options in ESCC [88]. A case report of ESCC on the number of CTCs before and after surgery and during follow-up over the course of five years suggested that monitoring CTC count could help in monitoring the disease progression and treatment efficacy [89]. The morphological technique by using the Cell Search System (CSS) could able to identify viable tumor cells from peripheral blood of ESCC. These findings suggest that the detection of CTCs might be a useful tool for predicting tumor progression and prognosis in patients with ESCC [90].