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Cancers
Special Issues
Roles of the Tumor Microenvironment on Liquid Biopsy
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Roles of the Tumor Microenvironment on Liquid Biopsy

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Tumor Microenvironment".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 8226

Special Issue Editor

Prof. Dr. Dario Marchetti

E-Mail Website
Guest Editor
1. Division of Molecular Medicine, Department of Internal Medicine, The University of New Mexico Health Sciences Center, Albuquerque, NM 87120, USA
2. Department of Pathology, The University of New Mexico Health Sciences Center, Albuquerque, NM 87120, USA
3. Full Member, UNM Comprehensive Cancer Center, Albuquerque, NM 87131, USA
Interests: the biology and therapeutic utility of circulating tumor cells (CTCs); liquid biopsies; mechanisms of brain metastasis and dormancy in breast and melanoma cancers; molecular crosstalks between dormant bone-marrow (BM) cells and CTCs; roles of BM and BM cellular heterogeneity interplaying with metastasis and dormancy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Cancer metastasis is the major cause of patient mortality and remains a daunting problem, both biologically and clinically. Although many advances have been made deciphering cancer in the circulation, mechanistic understandings and precise underpinnings of crosstalk between circulatory tumor and normal cells, setting the stage for metastasis, remains unknown. Historically, the enumeration of EpCAM-positive circulating tumor cells (CTCs) has allowed clinicians to estimate the overall metastatic burden in cancer patients, acting as an independent prognostic indicator of overall/progression-free survival of metastatic patients (“Liquid Biopsy”). However, thorough understanding of CTCs, CTC biomarkers and pathways, and CTC interactions with the tumor microenvironment, either in blood, bone marrow, or at organ sites is necessary for early detection and evaluation of treatment responses. The same can be applicable to other blood analytes (ctDNA, exosomes/extracellular vesicles, circulating microRNAs, etc.), to implement liquid biopsy clinically as an opportunity to monitor the evolutionary dynamics of cancer. Liquid biopsy represents a more conducive way to diagnose cancer patients compared to painful tumor biopsies, one of the most promising aspects of modern translational research, and is an inflection point toward precision cancer medicine. However, significant clinical, biological, and technical challenges remain identifying and interrogating CTC heterogeneity, CTC signatures associated with metastatic organ specificity, the standardization of ctDNA tests for clinical utility, clinically relevant roles played by exosomes and/or extracellular vesicles, and others. These challenges must be overcome to fulfill the promise of liquid biopsy for early-cancer detection, cancer screening and monitoring, assessing minimal residual disease, and for developing clinically useful tools for therapy effectiveness. The objective of this Special Issue is to publish the latest advances in CTC/liquid biopsy research and translational/clinical implementation. Contributions outlining discoveries in biological and clinical settings to foster these topics, including theoretical, technical, and preclinical models, are welcome.

Prof. Dr. Dario Marchetti
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Liquid biopsy
  • CTCs, CTC characterization and CTC clustering
  • ctDNA and ctDNA profiling
  • Exosomes/extracellular vesicles and biology
  • Tumor microenvironment
  • Bone marrow cellular/molecular heterogeneity
  • CTCs/blood/BM cells crosstalk
  • Analytical validity, clinical validity, and clinical utility of liquid biopsy
  • Liquid biopsy interplaying dormancy and metastasis

Published Papers (2 papers)

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Research

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21 pages, 4016 KiB  
Article
The Stroma Liquid Biopsy Panel Contains a Stromal-Epithelial Gene Signature Ratio That Is Associated with the Histologic Tumor-Stroma Ratio and Predicts Survival in Colon Cancer
by Cor J. Ravensbergen, Matthew Kuruc, Meaghan Polack, Stijn Crobach, Hein Putter, Hans Gelderblom, Devjit Roy, Rob A. E. M. Tollenaar and Wilma E. Mesker
Cancers 2022, 14(1), 163; https://doi.org/10.3390/cancers14010163 - 29 Dec 2021
Cited by 5 | Viewed by 1862
Abstract
Liquid biopsy has emerged as a novel approach to tumor characterization, offering advantages in sample accessibility and tissue heterogeneity. However, as mutational analysis predominates, the tumor microenvironment has largely remained unacknowledged in liquid biopsy research. The current work provides an explorative transcriptomic characterization [...] Read more.
Liquid biopsy has emerged as a novel approach to tumor characterization, offering advantages in sample accessibility and tissue heterogeneity. However, as mutational analysis predominates, the tumor microenvironment has largely remained unacknowledged in liquid biopsy research. The current work provides an explorative transcriptomic characterization of the Stroma Liquid BiopsyTM (SLB) proteomics panel in colon carcinoma by integrating single-cell and bulk transcriptomics data from publicly available repositories. Expression of SLB genes was significantly enriched in tumors with high histologic stromal content in comparison to tumors with low stromal content (median enrichment score 0.308 vs. 0.222, p = 0.036). In addition, we identified stromal-specific and epithelial-specific expression of the SLB genes, that was subsequently integrated into a gene signature ratio. The stromal-epithelial signature ratio was found to have prognostic significance in a discovery cohort of 359 colon adenocarcinoma patients (OS HR 2.581, 95%CI 1.567–4.251, p < 0.001) and a validation cohort of 229 patients (OS HR 2.590, 95%CI 1.659–4.043, p < 0.001). The framework described here provides transcriptomic evidence for the prognostic significance of the SLB panel constituents in colon carcinoma. Plasma protein levels of the SLB panel may reflect histologic intratumoral stromal content, a poor prognostic tumor characteristic, and hence provide valuable prognostic information in liquid biopsy. Full article
(This article belongs to the Special Issue Roles of the Tumor Microenvironment on Liquid Biopsy)
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Review

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23 pages, 1404 KiB  
Review
Dangerous Liaisons: Circulating Tumor Cells (CTCs) and Cancer-Associated Fibroblasts (CAFs)
by Pablo Hurtado, Inés Martínez-Pena and Roberto Piñeiro
Cancers 2020, 12(10), 2861; https://doi.org/10.3390/cancers12102861 - 05 Oct 2020
Cited by 49 | Viewed by 5335
Abstract
The crosstalk between cancer cells and the tumor microenvironment (TME) is a key determinant of cancer metastasis. Cancer-associated fibroblasts (CAFs), one of the main cellular components of TME, promote cancer cell invasion and dissemination through mechanisms including cell-cell interactions and the paracrine secretion [...] Read more.
The crosstalk between cancer cells and the tumor microenvironment (TME) is a key determinant of cancer metastasis. Cancer-associated fibroblasts (CAFs), one of the main cellular components of TME, promote cancer cell invasion and dissemination through mechanisms including cell-cell interactions and the paracrine secretion of growth factors, cytokines and chemokines. During metastasis, circulating tumor cells (CTCs) are shed from the primary tumor to the bloodstream, where they can be detected as single cells or clusters. The current knowledge about the biology of CTC clusters positions them as key actors in metastasis formation. It also indicates that CTCs do not act alone and that they may be aided by stromal and immune cells, which seem to shape their metastatic potential. Among these cells, CAFs are found associated with CTCs in heterotypic CTC clusters, and their presence seems to increase their metastatic efficiency. In this review, we summarize the current knowledge on the role that CAFs play on metastasis and we discuss their implication on the biogenesis, metastasis-initiating capacity of CTC clusters, and clinical implications. Moreover, we speculate about possible therapeutic strategies aimed to limit the metastatic potential of CTC clusters involving the targeting of CAFs as well as their difficulties and limitations. Full article
(This article belongs to the Special Issue Roles of the Tumor Microenvironment on Liquid Biopsy)
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