Advances in Development and Spread of Cancer

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 8375

Special Issue Editor


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Guest Editor
Institute for Experimental Endocrinology and Oncology "G. Salvatore" (IEOS) - Second Unit, National Research Council, Via Pietro Castellino 111, 80131 Naples, Italy
Interests: molecular oncology; cellular and molecular biology; biochemistry; golgi complex; GRASP65
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Special Issue Information

Dear Colleagues,

Over the past decades, several studies have argued that the accumulation of both genetic and epigenetic alterations and the molecular and signalling pathways alterations determines the intrinsic properties of the cancer cells thus leading to cancer development and spread. Afterwards, the cancer cell-centred view of tumour biology has been challenged by the study of the tumour microenvironment, which has highlighted that cancer progression is also the result of the bidirectional and dynamic complex of interactions between the cancer cells and the stromal cells in the tumour microenvironment. Tumour cells co-evolve with several specialized tissue-resident and/or recruited cells which, working in concert, generate an environment favourable for cancer cells' growth, survival, metastatic spread and colonization at distant sites. Similarly, cancer cells derived exosomes contribute to establishing a cancer-permissive microenvironment and promote cancer malignant phenotype. In addition, recent evidence has demonstrated that microbiota contributes to carcinogenesis, mainly by influencing host cell proliferation and death, altering immune system activity, and affecting host metabolism. All together these lines of evidence suggest that cancer development and spread are complex processes involving multiple players.

In this Special Issue of Cells, I would like to include original research and review articles that contribute to the further unravelling of the molecular mechanisms underlying cancer development and spread. All scientists working in this field are cordially invited to submit their manuscripts.

Dr. Daniela Spano
Guest Editor

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Keywords

  • cancer genetics and epigenetics
  • molecular and signaling pathways
  • tumor microenvironment
  • microbiota
  • exosomes

Published Papers (5 papers)

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Research

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15 pages, 4981 KiB  
Article
Characterization of Three Somatic Mutations in the 3′UTR of RRAS2 and Their Inverse Correlation with Lymphocytosis in Chronic Lymphocytic Leukemia
by Marta Lacuna, Alejandro M. Hortal, Claudia Cifuentes, Tania Gonzalo, Miguel Alcoceba, Miguel Bastos, Xosé R. Bustelo, Marcos González and Balbino Alarcón
Cells 2023, 12(23), 2687; https://doi.org/10.3390/cells12232687 - 22 Nov 2023
Viewed by 880
Abstract
Chronic lymphocytic leukemia (CLL) is a hematologic malignancy characterized by progressive accumulation of a rare population of CD5+ B-lymphocytes in peripheral blood, bone marrow, and lymphoid tissues. CLL exhibits remarkable clinical heterogeneity, with some patients presenting with indolent disease and others progressing rapidly [...] Read more.
Chronic lymphocytic leukemia (CLL) is a hematologic malignancy characterized by progressive accumulation of a rare population of CD5+ B-lymphocytes in peripheral blood, bone marrow, and lymphoid tissues. CLL exhibits remarkable clinical heterogeneity, with some patients presenting with indolent disease and others progressing rapidly to aggressive CLL. The significant heterogeneity of CLL underscores the importance of identifying novel prognostic markers. Recently, the RAS-related gene RRAS2 has emerged as both a driver oncogene and a potential marker for CLL progression, with higher RRAS2 expression associated with poorer disease prognosis. Although missense somatic mutations in the coding sequence of RRAS2 have not been described in CLL, this study reports the frequent detection of three somatic mutations in the 3′ untranslated region (3′UTR) affecting positions +26, +53, and +180 downstream of the stop codon in the mRNA. An inverse relationship was observed between these three somatic mutations and RRAS2 mRNA expression, which correlated with lower blood lymphocytosis. These findings highlight the importance of RRAS2 overexpression in CLL development and prognosis and point to somatic mutations in its 3′UTR as novel mechanistic clues. Our results may contribute to the development of targeted therapeutic strategies and improved risk stratification for CLL patients. Full article
(This article belongs to the Special Issue Advances in Development and Spread of Cancer)
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Review

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23 pages, 2283 KiB  
Review
The Complex Role of the Microbiome in Non-Small Cell Lung Cancer Development and Progression
by Vanessa G. P. Souza, Aisling Forder, Michelle E. Pewarchuk, Nikita Telkar, Rachel Paes de Araujo, Greg L. Stewart, Juliana Vieira, Patricia P. Reis and Wan L. Lam
Cells 2023, 12(24), 2801; https://doi.org/10.3390/cells12242801 - 8 Dec 2023
Cited by 1 | Viewed by 1875
Abstract
In recent years, there has been a growing interest in the relationship between microorganisms in the surrounding environment and cancer cells. While the tumor microenvironment predominantly comprises cancer cells, stromal cells, and immune cells, emerging research highlights the significant contributions of microbial cells [...] Read more.
In recent years, there has been a growing interest in the relationship between microorganisms in the surrounding environment and cancer cells. While the tumor microenvironment predominantly comprises cancer cells, stromal cells, and immune cells, emerging research highlights the significant contributions of microbial cells to tumor development and progression. Although the impact of the gut microbiome on treatment response in lung cancer is well established, recent investigations indicate complex roles of lung microbiota in lung cancer. This article focuses on recent findings on the human lung microbiome and its impacts in cancer development and progression. We delve into the characteristics of the lung microbiome and its influence on lung cancer development. Additionally, we explore the characteristics of the intratumoral microbiome, the metabolic interactions between lung tumor cells, and how microorganism-produced metabolites can contribute to cancer progression. Furthermore, we provide a comprehensive review of the current literature on the lung microbiome and its implications for the metastatic potential of tumor cells. Additionally, this review discusses the potential for therapeutic modulation of the microbiome to establish lung cancer prevention strategies and optimize lung cancer treatment. Full article
(This article belongs to the Special Issue Advances in Development and Spread of Cancer)
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11 pages, 1347 KiB  
Review
TEM8 in Oncogenesis: Protein Biology, Pre-Clinical Agents, and Clinical Rationale
by Samuel A. Kareff, Virginia Corbett, Paul Hallenbeck and Aman Chauhan
Cells 2023, 12(22), 2623; https://doi.org/10.3390/cells12222623 - 14 Nov 2023
Viewed by 1611
Abstract
The TEM8 protein represents an emerging biomarker in many solid tumor histologies. Given the various roles it plays in oncogenesis, including but not limited to angiogenesis, epithelial-to-mesenchymal transition, and cell migration, TEM8 has recently served and will continue to serve as the target [...] Read more.
The TEM8 protein represents an emerging biomarker in many solid tumor histologies. Given the various roles it plays in oncogenesis, including but not limited to angiogenesis, epithelial-to-mesenchymal transition, and cell migration, TEM8 has recently served and will continue to serve as the target of novel oncologic therapies. We review herein the role of TEM8 in oncogenesis. We review its normal function, highlight the additional roles it plays in the tumor microenvironment, and synthesize pre-clinical and clinical data currently available. We underline the protein’s prognostic and predictive abilities in various solid tumors by (1) highlighting its association with more aggressive disease biology and poor clinical outcomes and (2) assessing its associated clinical trial landscape. Finally, we offer future directions for clinical studies involving TEM8, including incorporating pre-clinical agents into clinical trials and combining previously tested oncologic therapies with currently available treatments, such as immunotherapy. Full article
(This article belongs to the Special Issue Advances in Development and Spread of Cancer)
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20 pages, 1519 KiB  
Review
Developing Oncolytic Viruses for the Treatment of Cervical Cancer
by Eleni Kalafati, Ekati Drakopoulou, Nicholas P. Anagnou and Kalliopi I. Pappa
Cells 2023, 12(14), 1838; https://doi.org/10.3390/cells12141838 - 13 Jul 2023
Cited by 2 | Viewed by 1669
Abstract
Cervical cancer represents one of the most important malignancies among women worldwide. Current therapeutic approaches for cervical cancer are reported not only to be inadequate for metastatic cervical cancer, but are also considered as cytotoxic for several patients leading to serious side effects, [...] Read more.
Cervical cancer represents one of the most important malignancies among women worldwide. Current therapeutic approaches for cervical cancer are reported not only to be inadequate for metastatic cervical cancer, but are also considered as cytotoxic for several patients leading to serious side effects, which can have negative implications on the quality of life of women. Therefore, there is an urgent need for the development of innovative and effective treatment options. Oncolytic viruses can eventually become effective biological agents, since they preferentially infect and kill cancer cells, while leaving the normal tissue unaffected. Moreover, they are also able to leverage the host immune system response to limit tumor growth. This review aims to systematically describe and discuss the different types of oncolytic viruses generated for targeting cervical cancer cells, as well as the outcome of the combination of virotherapy with conventional therapies. Although many preclinical studies have evaluated the therapeutic efficacy of oncolytic viruses in cervical cancer, the number of clinical trials so far is limited, while their oncolytic properties are currently being tested in clinical trials for the treatment of other malignancies. Full article
(This article belongs to the Special Issue Advances in Development and Spread of Cancer)
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Other

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25 pages, 1668 KiB  
Perspective
Targeting the Ubiquitin–Proteasome System and Recent Advances in Cancer Therapy
by Daniela Spano and Giuliana Catara
Cells 2024, 13(1), 29; https://doi.org/10.3390/cells13010029 - 22 Dec 2023
Cited by 2 | Viewed by 1752
Abstract
Ubiquitination is a reversible post-translational modification based on the chemical addition of ubiquitin to proteins with regulatory effects on various signaling pathways. Ubiquitination can alter the molecular functions of tagged substrates with respect to protein turnover, biological activity, subcellular localization or protein–protein interaction. [...] Read more.
Ubiquitination is a reversible post-translational modification based on the chemical addition of ubiquitin to proteins with regulatory effects on various signaling pathways. Ubiquitination can alter the molecular functions of tagged substrates with respect to protein turnover, biological activity, subcellular localization or protein–protein interaction. As a result, a wide variety of cellular processes are under ubiquitination-mediated control, contributing to the maintenance of cellular homeostasis. It follows that the dysregulation of ubiquitination reactions plays a relevant role in the pathogenic states of human diseases such as neurodegenerative diseases, immune-related pathologies and cancer. In recent decades, the enzymes of the ubiquitin–proteasome system (UPS), including E3 ubiquitin ligases and deubiquitinases (DUBs), have attracted attention as novel druggable targets for the development of new anticancer therapeutic approaches. This perspective article summarizes the peculiarities shared by the enzymes involved in the ubiquitination reaction which, when deregulated, can lead to tumorigenesis. Accordingly, an overview of the main pharmacological interventions based on targeting the UPS that are in clinical use or still in clinical trials is provided, also highlighting the limitations of the therapeutic efficacy of these approaches. Therefore, various attempts to circumvent drug resistance and side effects as well as UPS-related emerging technologies in anticancer therapeutics are discussed. Full article
(This article belongs to the Special Issue Advances in Development and Spread of Cancer)
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