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Cancers
Special Issues
Tumor Heterogeneity: Recent Trends and Current Issues
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Tumor Heterogeneity: Recent Trends and Current Issues

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

Deadline for manuscript submissions: closed (20 February 2023) | Viewed by 18237

Special Issue Editors

Prof. Dr. Bahriye Aktas

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Guest Editor
University of Leipzig, Medical Center, Dept. of Gynaecology, Leipzig, Germany
Dr. Ivonne Nel

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Guest Editor
University of Leipzig, Research Lab, Dept. of Gynaecology, Leipzig, Germany

Special Issue Information

Dear Colleagues,

Heterogeneity among cancer cells within one tumor and metastases thereof has gained increased attention particularly concerning the treatment of mamma carcinoma and gynecological malignancies such as ovarian cancer. Next to morphological and metabolic changes, different phenotypical profiles and altered genetic patterns, tumor cells exhibit diversification of motility, proliferation and metastatic potential. Hence, tumor heterogeneity plays a key role in cancer diagnosis, treatment choice, therapy response and patient outcome. Extremely heterogonous tumors are associated with aggressive behavior and treatment resistance. Deeper insight into mechanisms that drive tumor heterogeneity might help to identify novel treatment strategies and therapeutic targets.

The Special Issue “Tumor heterogeneity” seeks to broaden the knowledge concerning crucial changes at various cellular and molecular levels that may influence carcinogenesis and prognosis. This Special Issue intends to publish original research articles, reviews and methodological papers.

Prof. Dr. Bahriye Aktas
Dr. Ivonne Nel
Guest Editors

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 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

  • Heterogeneity
  • Gynecological malignancies
  • breast cancer
  • receptor discordance
  • metastasis
  • mutation
  • resistance

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Published Papers (5 papers)

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Research

Jump to: Review

13 pages, 1948 KiB  
Article
Heterogeneity between Core Needle Biopsy and Synchronous Axillary Lymph Node Metastases in Early Breast Cancer Patients—A Comparison of HER2, Estrogen and Progesterone Receptor Expression Profiles during Primary Treatment Regime
by Laura Weydandt, Ivonne Nel, Anne Kreklau, Lars-Christian Horn and Bahriye Aktas
Cancers 2022, 14(8), 1863; https://doi.org/10.3390/cancers14081863 - 7 Apr 2022
Cited by 7 | Viewed by 2030
Abstract
In breast cancer therapeutic decisions are based on the expression of estrogen (ER), progesterone (PR), the human epidermal growth factor 2 (HER2) receptors and the proliferation marker Ki67. However, only little is known concerning heterogeneity between the primary tumor and axillary lymph node [...] Read more.
In breast cancer therapeutic decisions are based on the expression of estrogen (ER), progesterone (PR), the human epidermal growth factor 2 (HER2) receptors and the proliferation marker Ki67. However, only little is known concerning heterogeneity between the primary tumor and axillary lymph node metastases (LNM) in the primary site. We retrospectively analyzed receptor profiles of 215 early breast cancer patients with axillary synchronous LNM. Of our cohort, 69% were therapy naive and did not receive neoadjuvant treatment. Using immunohistochemistry, receptor status and Ki67 were compared between core needle biopsy of the tumor (t-CNB) and axillary LNM obtained during surgery. The discordance rates between t-CNB and axillary LNM were 12% for HER2, 6% for ER and 20% for PR. Receptor discordance appears to already occur at the primary site. Receptor losses might play a role concerning overtreatment concomitant with adverse drug effects, while receptor gains might be an option for additional targeted or endocrine therapy. Hence, not only receptor profiles of the tumor tissue but also of the synchronous axillary LNM should be considered in the choice of treatment. Full article
(This article belongs to the Special Issue Tumor Heterogeneity: Recent Trends and Current Issues)
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17 pages, 3835 KiB  
Article
Towards a Better Characterisation of Leukemic Cells in Chronic Lymphocytic Leukaemia: Cell-Size Heterogeneity Reflects Their Activation Status and Migratory Abilities
by Gayane Manukyan, Zuzana Mikulkova, Peter Turcsanyi, Jakub Savara, Markéta Trajerová, Zuzana Kubova, Tomas Papajik and Eva Kriegova
Cancers 2021, 13(19), 4922; https://doi.org/10.3390/cancers13194922 - 30 Sep 2021
Cited by 3 | Viewed by 2889
Abstract
Chronic lymphocytic leukaemia (CLL) is a genetically, morphologically and phenotypically heterogeneous chronic disease with clinical variability between patients. Whether the significant heterogeneity of cell size within the CLL population contributes to the heterogeneous features of this disease has not been investigated. The present [...] Read more.
Chronic lymphocytic leukaemia (CLL) is a genetically, morphologically and phenotypically heterogeneous chronic disease with clinical variability between patients. Whether the significant heterogeneity of cell size within the CLL population contributes to the heterogeneous features of this disease has not been investigated. The present study aimed to characterise the phenotypic and functional properties of two subpopulations of typical CLL cells that differ in cell size: small (s-CLL) and large (l-CLL) CLL cells delineated by forward scatter cytometry. The s-CLL cells were characterised by the CD5lowCXCR4hi phenotype, while the l-CLL cells were characterised by the CD5hiCXCR4dim phenotype and indicated a higher expression of CXCR3, CD20, CD38 and HLA-DR. The l-CLL cells displayed higher migration activity towards CXCL12, a tendency towards a higher proliferation rate and an increased capacity to produce IgM in the presence of CpG compared with s-CLL cells. When stimulated with CpG and CXCL12, l-CLL cells were characterised by a higher polarisation phenotype and motility than s-CLL cells. Our study revealed that the differences in CLL cell size reflected their activation status, polarisation and migratory abilities. Our data provide evidence of the importance of cell-size heterogeneity within a CLL pool and the dynamics of cell-size changes for disease pathogenesis, thus deserving further investigation. Full article
(This article belongs to the Special Issue Tumor Heterogeneity: Recent Trends and Current Issues)
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18 pages, 4336 KiB  
Article
The Mechanical Fingerprint of Circulating Tumor Cells (CTCs) in Breast Cancer Patients
by Ivonne Nel, Erik W. Morawetz, Dimitrij Tschodu, Josef A. Käs and Bahriye Aktas
Cancers 2021, 13(5), 1119; https://doi.org/10.3390/cancers13051119 - 5 Mar 2021
Cited by 9 | Viewed by 3219
Abstract
Circulating tumor cells (CTCs) are a potential predictive surrogate marker for disease monitoring. Due to the sparse knowledge about their phenotype and its changes during cancer progression and treatment response, CTC isolation remains challenging. Here we focused on the mechanical characterization of circulating [...] Read more.
Circulating tumor cells (CTCs) are a potential predictive surrogate marker for disease monitoring. Due to the sparse knowledge about their phenotype and its changes during cancer progression and treatment response, CTC isolation remains challenging. Here we focused on the mechanical characterization of circulating non-hematopoietic cells from breast cancer patients to evaluate its utility for CTC detection. For proof of premise, we used healthy peripheral blood mononuclear cells (PBMCs), human MDA-MB 231 breast cancer cells and human HL-60 leukemia cells to create a CTC model system. For translational experiments CD45 negative cells—possible CTCs—were isolated from blood samples of patients with mamma carcinoma. Cells were mechanically characterized in the optical stretcher (OS). Active and passive cell mechanical data were related with physiological descriptors by a random forest (RF) classifier to identify cell type specific properties. Cancer cells were well distinguishable from PBMC in cell line tests. Analysis of clinical samples revealed that in PBMC the elliptic deformation was significantly increased compared to non-hematopoietic cells. Interestingly, non-hematopoietic cells showed significantly higher shape restoration. Based on Kelvin–Voigt modeling, the RF algorithm revealed that elliptic deformation and shape restoration were crucial parameters and that the OS discriminated non-hematopoietic cells from PBMC with an accuracy of 0.69, a sensitivity of 0.74, and specificity of 0.63. The CD45 negative cell population in the blood of breast cancer patients is mechanically distinguishable from healthy PBMC. Together with cell morphology, the mechanical fingerprint might be an appropriate tool for marker-free CTC detection. Full article
(This article belongs to the Special Issue Tumor Heterogeneity: Recent Trends and Current Issues)
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Review

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18 pages, 1002 KiB  
Review
Cancer Stem Cells in Tumor Microenvironment of Adenocarcinoma of the Stomach, Colon, and Rectum
by Jose Francisco Islas, Adriana G. Quiroz-Reyes, Paulina Delgado-Gonzalez, Hector Franco-Villarreal, Juan Luis Delgado-Gallegos, Elsa N. Garza-Treviño and Carlos A. Gonzalez-Villarreal
Cancers 2022, 14(16), 3948; https://doi.org/10.3390/cancers14163948 - 16 Aug 2022
Cited by 3 | Viewed by 2515
Abstract
Gastrointestinal adenocarcinomas are one of the world’s deadliest cancers. Cancer stem cells and the tissue microenvironment are highly regulated by cell and molecular mechanisms. Cancer stem cells are essential for maintenance and progression and are associated with resistance to conventional treatments. This article [...] Read more.
Gastrointestinal adenocarcinomas are one of the world’s deadliest cancers. Cancer stem cells and the tissue microenvironment are highly regulated by cell and molecular mechanisms. Cancer stem cells are essential for maintenance and progression and are associated with resistance to conventional treatments. This article reviews the current knowledge of the role of the microenvironment during the primary establishment of gastrointestinal adenocarcinomas in the stomach, colon, and rectum and its relationship with cancer stem cells. We also describe novel developments in cancer therapeutics, such as targeted therapy, and discuss the advantages and disadvantages of different treatments for improving gastrointestinal cancer prognosis. Full article
(This article belongs to the Special Issue Tumor Heterogeneity: Recent Trends and Current Issues)
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28 pages, 4053 KiB  
Review
A Tale of Two Cancers: A Current Concise Overview of Breast and Prostate Cancer
by Franklyn De Silva and Jane Alcorn
Cancers 2022, 14(12), 2954; https://doi.org/10.3390/cancers14122954 - 15 Jun 2022
Cited by 28 | Viewed by 6554
Abstract
Cancer is a global issue, and it is expected to have a major impact on our continuing global health crisis. As populations age, we see an increased incidence in cancer rates, but considerable variation is observed in survival rates across different geographical regions [...] Read more.
Cancer is a global issue, and it is expected to have a major impact on our continuing global health crisis. As populations age, we see an increased incidence in cancer rates, but considerable variation is observed in survival rates across different geographical regions and cancer types. Both breast and prostate cancer are leading causes of morbidity and mortality worldwide. Although cancer statistics indicate improvements in some areas of breast and prostate cancer prevention, diagnosis, and treatment, such statistics clearly convey the need for improvements in our understanding of the disease, risk factors, and interventions to improve life span and quality of life for all patients, and hopefully to effect a cure for people living in developed and developing countries. This concise review compiles the current information on statistics, pathophysiology, risk factors, and treatments associated with breast and prostate cancer. Full article
(This article belongs to the Special Issue Tumor Heterogeneity: Recent Trends and Current Issues)
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