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Cancers
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Experimental and Clinical Advances in Counteracting Progression of Solid Cancers
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Experimental and Clinical Advances in Counteracting Progression of Solid Cancers

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 45060

Special Issue Editors

Dr. Paola Ferrari

E-Mail Website
Guest Editor
Department of Clinical and Experimental Medicine, Azienda Ospedaliero-Universitaria Pisana (AOUP), via Roma 67, 56126 Pisa, Italy
Interests: breast and gastrointestinal cancer follow-up and therapy; breast cancer biomarkers and prognostic factors; cancer immunology; circulating tumor cells; cancer stem cells
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Andrea Nicolini

E-Mail Website
Guest Editor
Department of Internal Medicine, University of Pisa, Santa Chiara Hospital, via Roma 67, 56126 Pisa, Italy
Interests: breast and gastrointestinal cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer is a complex and hard to face genetic disease. The current model describes sustaining proliferative signalling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, reprogramming energy and metabolism and evading immune destruction the principal hallmarks promoting cancer progression. All of them occur in the context of chronic inflammation and genomic instability, two additional, more recently defined hallmarks. Moreover, the cross-talk between cancer cell and tumor microenvironment significantly contributes to cancer evolution. Detectable metastatic disease is commonly uncurable and accounts for most cancer deaths. Understanding the genetic and biological mechanisms sustaining progression from cancer initiation to overt metastatic disease is crucial to efficaciously contrast cancer disease. Although a long way has been run, cancer remains a "work in progress" yard and a huge social problem and many expectations come from the recent advances in genetic technology, molecular biology and immunology-immunotherapy. Any experimental and clinical work potentially relevant to this special issue will be carefully considered for inclusion.

Dr. Paola Ferrari
Prof. Dr. Andrea Nicolini
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 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

  • solid cancers
  • cancer progression
  • tumor cross-talk
  • cancer genetics
  • cancer molecular biology
  • cancer immunology
  • cancer immunotherapy

Published Papers (10 papers)

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Editorial

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3 pages, 170 KiB  
Editorial
Experimental and Clinical Advances in Counteracting Progression of Solid Cancers
by Andrea Nicolini
Cancers 2023, 15(7), 1956; https://doi.org/10.3390/cancers15071956 - 24 Mar 2023
Viewed by 724
Abstract
In recent decades, impressing technological developments have significantly advanced our understanding of cancer [...] Full article
(This article belongs to the Special Issue Experimental and Clinical Advances in Counteracting Progression of Solid Cancers)

Research

Jump to: Editorial, Review, Other

12 pages, 1051 KiB  
Article
A Drug Screening Revealed Novel Potential Agents against Malignant Pleural Mesothelioma
by Irene Dell’Anno, Alessandra Melani, Sarah A. Martin, Marcella Barbarino, Roberto Silvestri, Monica Cipollini, Antonio Giordano, Luciano Mutti, Andrea Nicolini, Luca Luzzi, Raffaele Aiello, Federica Gemignani and Stefano Landi
Cancers 2022, 14(10), 2527; https://doi.org/10.3390/cancers14102527 - 20 May 2022
Cited by 8 | Viewed by 3217
Abstract
The lack of effective therapies remains one of the main challenges for malignant pleural mesothelioma (MPM). In this perspective, drug repositioning could accelerate the identification of novel treatments. We screened 1170 FDA-approved drugs on a SV40-immortalized mesothelial (MeT-5A) and five MPM (Mero-14, Mero-25, [...] Read more.
The lack of effective therapies remains one of the main challenges for malignant pleural mesothelioma (MPM). In this perspective, drug repositioning could accelerate the identification of novel treatments. We screened 1170 FDA-approved drugs on a SV40-immortalized mesothelial (MeT-5A) and five MPM (Mero-14, Mero-25, IST-Mes2, NCI-H28 and MSTO-211H) cell lines. Biological assays were carried out for 41 drugs, showing the highest cytotoxicity and for whom there were a complete lack of published literature in MPM. Cytotoxicity and caspase activation were evaluated with commercially available kits and cell proliferation was assayed using MTT assay and by clonogenic activity with standard protocols. Moreover, the five most effective drugs were further evaluated on patient-derived primary MPM cell lines. The most active molecules were cephalomannine, ouabain, alexidine, thonzonium bromide, and emetine. Except for alexidine, these drugs inhibited the clonogenic ability and caspase activation in all cancer lines tested. The proliferation was inhibited also on an extended panel of cell lines, including primary MPM cells. Thus, we suggest that cephalomannine, ouabain, thonzonium bromide, and emetine could represent novel candidates to be repurposed for improving the arsenal of therapeutic weapons in the fight against MPM. Full article
(This article belongs to the Special Issue Experimental and Clinical Advances in Counteracting Progression of Solid Cancers)
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13 pages, 582 KiB  
Article
Diagnostic Validation of a Comprehensive Targeted Panel for Broad Mutational and Biomarker Analysis in Solid Tumors
by Guy Froyen, Ellen Geerdens, Severine Berden, Bert Cruys and Brigitte Maes
Cancers 2022, 14(10), 2457; https://doi.org/10.3390/cancers14102457 - 16 May 2022
Cited by 8 | Viewed by 3502
Abstract
The use of targeted Next Generation Sequencing (NGS) for the diagnostic screening of somatic variants in solid tumor samples has proven its high clinical value. Because of the large number of ongoing clinical trials for a multitude of variants in a growing number [...] Read more.
The use of targeted Next Generation Sequencing (NGS) for the diagnostic screening of somatic variants in solid tumor samples has proven its high clinical value. Because of the large number of ongoing clinical trials for a multitude of variants in a growing number of genes, as well as the detection of proven and emerging pan-cancer biomarkers including microsatellite instability (MSI) and tumor mutation burden (TMB), the currently employed diagnostic gene panels will become vastly insufficient in the near future. Here, we describe the validation and implementation of the hybrid capture-based comprehensive TruSight Oncology (TSO500) assay that is able to detect single-nucleotide variants (SNVs) and subtle deletions and insertions (indels) in 523 tumor-associated genes, copy-number variants (CNVs) of 69 genes, fusions with 55 cancer driver genes, and MSI and TMB. Extensive validation of the TSO500 assay was performed on DNA or RNA from 170 clinical samples with neoplastic content down to 10%, using multiple tissue and specimen types. Starting with 80 ng DNA and 40 ng RNA extracted from formalin-fixed and paraffine-embedded (FFPE) samples revealed a precision and accuracy >99% for all variant types. The analytical sensitivity and specificity were at least 99% for SNVs, indels, CNVs, MSI, and gene rearrangements. For TMB, only values around the threshold could yield a deviating outcome. The limit-of-detection for SNVs and indels was well below the set threshold of 5% variant allele frequency (VAF). This validated comprehensive genomic profiling assay was then used to screen 624 diagnostic samples, and its success rate for adoption in a clinical diagnostic setting of broad solid tumor screening was assessed on this cohort. Full article
(This article belongs to the Special Issue Experimental and Clinical Advances in Counteracting Progression of Solid Cancers)
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15 pages, 4543 KiB  
Article
Reflector-Guided Localisation of Non-Palpable Breast Lesions: A Prospective Evaluation of the SAVI SCOUT® System
by Umar Wazir, Iham Kasem, Michael J. Michell, Tamara Suaris, David Evans, Anmol Malhotra and Kefah Mokbel
Cancers 2021, 13(10), 2409; https://doi.org/10.3390/cancers13102409 - 17 May 2021
Cited by 13 | Viewed by 4635
Abstract
Wire-guided localisation (WGL) has been the mainstay for localising non-palpable breast lesions before excision. Due to its limitations, various wireless alternatives have been developed. In this prospective study, we evaluate the role of radiation-free wireless localisation using the SAVI SCOUT® system at [...] Read more.
Wire-guided localisation (WGL) has been the mainstay for localising non-palpable breast lesions before excision. Due to its limitations, various wireless alternatives have been developed. In this prospective study, we evaluate the role of radiation-free wireless localisation using the SAVI SCOUT® system at the London Breast Institute. A total of 72 reflectors were deployed in 67 consecutive patients undergoing breast conserving surgery for non-palpable breast lesions. The mean interval between deployment and surgery for the therapeutic cases was 18.8 days (range: 0–210). The median deployment duration was 5 min (range: 1–15 min). The mean distance from the lesion was 1.1 mm (median distance: 0; range: 0–20 mm). The rate of surgical localisation and retrieval of the reflector was 98.6% and 100%, respectively. The median operating time was 28 min (range: 15–55 min) for the therapeutic excision of malignancy and 17 min (range: 15–24) for diagnostic excision. The incidence of reflector migration was 0%. Radial margin positivity in malignant cases was 7%. The median weight for malignant lesions was 19.6 g (range: 3.5–70 g). Radiologists and surgeons rated the system higher than WGL (93.7% and 98.6%, respectively; 60/64 and 70/71). The patient mean satisfaction score was 9.7/10 (n = 47, median = 10; range: 7–10). One instance of signal failure was reported. In patients who had breast MRI after the deployment of the reflector, the MRI void signal was <5 mm (n = 6). There was no specific technique-related surgical complication. Our study demonstrates that wire-free localisation using SAVI SCOUT® is an effective and time-efficient alternative to WGL with excellent physician and patient acceptance. Full article
(This article belongs to the Special Issue Experimental and Clinical Advances in Counteracting Progression of Solid Cancers)
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18 pages, 2460 KiB  
Article
Assessment of PI3K/mTOR/AKT Pathway Elements to Serve as Biomarkers and Therapeutic Targets in Penile Cancer
by Anita Thomas, Sascha Reetz, Philipp Stenzel, Katrin Tagscherer, Wilfried Roth, Mario Schindeldecker, Martin Michaelis, Florian Rothweiler, Jindrich Cinatl, Jr., Jaroslav Cinatl, Robert Dotzauer, Olesya Vakhrusheva, Maarten Albersen, Stephan Macher-Goeppinger, Axel Haferkamp, Eva Juengel, Andreas Neisius and Igor Tsaur
Cancers 2021, 13(10), 2323; https://doi.org/10.3390/cancers13102323 - 12 May 2021
Cited by 7 | Viewed by 2299
Abstract
The PI3K/mTOR/AKT pathway might represent an intriguing option for treatment of penile cancer (PeCa). We aimed to assess whether members of this pathway might serve as biomarkers and targets for systemic therapy. Tissue of primary cancer from treatment-naïve PeCa patients was used for [...] Read more.
The PI3K/mTOR/AKT pathway might represent an intriguing option for treatment of penile cancer (PeCa). We aimed to assess whether members of this pathway might serve as biomarkers and targets for systemic therapy. Tissue of primary cancer from treatment-naïve PeCa patients was used for tissue microarray analysis. Immunohistochemical staining was performed with antibodies against AKT, pAKT, mTOR, pmTOR, pS6, pPRAS, p4EBP1, S6K1 and pp70S6K. Protein expression was correlated with clinicopathological characteristics as well as overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS) and metastasis-free survival (MFS). AKT inhibition was tested in two primarily established, treatment-naïve PeCa cell lines by treatment with capivasertib and analysis of cell viability and chemotaxis. A total of 76 patients surgically treated for invasive PeCa were included. Higher expression of AKT was significantly more prevalent in high-grade tumors and predictive of DSS and OS in the Kaplan–Meier analysis, and an independent predictor of worse OS and DSS in the multivariate regression analysis. Treatment with pan-AKT inhibitor capivasertib in PeCa cell lines induced a significant downregulation of both total AKT and pAKT as well as decreased cell viability and chemotaxis. Selected protein candidates of the mTOR/AKT signaling pathway demonstrate association with histological and survival parameters of PeCa patients, whereas AKT appears to be the most promising one. Full article
(This article belongs to the Special Issue Experimental and Clinical Advances in Counteracting Progression of Solid Cancers)
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Review

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20 pages, 1328 KiB  
Review
An Overview on the Histogenesis and Morphogenesis of Salivary Gland Neoplasms and Evolving Diagnostic Approaches
by Janaki Iyer, Arvind Hariharan, Uyen Minh Nha Cao, Crystal To Tam Mai, Athena Wang, Parisa Khayambashi, Bich Hong Nguyen, Lydia Safi and Simon D. Tran
Cancers 2021, 13(15), 3910; https://doi.org/10.3390/cancers13153910 - 03 Aug 2021
Cited by 28 | Viewed by 8784
Abstract
Salivary gland neoplasms (SGN) remain a diagnostic dilemma due to their heterogenic complex behavior. Their diverse histomorphological appearance is attributed to the underlying cellular mechanisms and differentiation into various histopathological subtypes with overlapping fea-tures. Diagnostic tools such as fine needle aspiration biopsy, computerized [...] Read more.
Salivary gland neoplasms (SGN) remain a diagnostic dilemma due to their heterogenic complex behavior. Their diverse histomorphological appearance is attributed to the underlying cellular mechanisms and differentiation into various histopathological subtypes with overlapping fea-tures. Diagnostic tools such as fine needle aspiration biopsy, computerized tomography, magnetic resonance imaging, and positron emission tomography help evaluate the structure and assess the staging of SGN. Advances in molecular pathology have uncovered genetic patterns and oncogenes by immunohistochemistry, fluorescent in situ hybridization, and next–generation sequencing, that may potentially contribute to innovating diagnostic approaches in identifying various SGN. Surgical resection is the principal treatment for most SGN. Other modalities such as radiotherapy, chemotherapy, targeted therapy (agents like tyrosine kinase inhibitors, monoclonal antibodies, and proteasome inhibitors), and potential hormone therapy may be applied, depending on the clinical behaviors, histopathologic grading, tumor stage and location, and the extent of tissue invasion. This review delves into the molecular pathways of salivary gland tumorigenesis, highlighting recent diagnostic protocols that may facilitate the identification and management of SGN. Full article
(This article belongs to the Special Issue Experimental and Clinical Advances in Counteracting Progression of Solid Cancers)
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Graphical abstract

29 pages, 906 KiB  
Review
Approaches to Enhance Natural Killer Cell-Based Immunotherapy for Pediatric Solid Tumors
by Aicha E. Quamine, Mallery R. Olsen, Monica M. Cho and Christian M. Capitini
Cancers 2021, 13(11), 2796; https://doi.org/10.3390/cancers13112796 - 04 Jun 2021
Cited by 14 | Viewed by 6871
Abstract
Treatment of metastatic pediatric solid tumors remain a significant challenge, particularly in relapsed and refractory settings. Standard treatment has included surgical resection, radiation, chemotherapy, and, in the case of neuroblastoma, immunotherapy. Despite such intensive therapy, cancer recurrence is common, and most tumors become [...] Read more.
Treatment of metastatic pediatric solid tumors remain a significant challenge, particularly in relapsed and refractory settings. Standard treatment has included surgical resection, radiation, chemotherapy, and, in the case of neuroblastoma, immunotherapy. Despite such intensive therapy, cancer recurrence is common, and most tumors become refractory to prior therapy, leaving patients with few conventional treatment options. Natural killer (NK) cells are non-major histocompatibility complex (MHC)-restricted lymphocytes that boast several complex killing mechanisms but at an added advantage of not causing graft-versus-host disease, making use of allogeneic NK cells a potential therapeutic option. On top of their killing capacity, NK cells also produce several cytokines and growth factors that act as key regulators of the adaptive immune system, positioning themselves as ideal effector cells for stimulating heavily pretreated immune systems. Despite this promise, clinical efficacy of adoptive NK cell therapy to date has been inconsistent, prompting a detailed understanding of the biological pathways within NK cells that can be leveraged to develop “next generation” NK cell therapies. Here, we review advances in current approaches to optimizing the NK cell antitumor response including combination with other immunotherapies, cytokines, checkpoint inhibition, and engineering NK cells with chimeric antigen receptors (CARs) for the treatment of pediatric solid tumors. Full article
(This article belongs to the Special Issue Experimental and Clinical Advances in Counteracting Progression of Solid Cancers)
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12 pages, 1001 KiB  
Review
Molecular Genetics of Follicular-Derived Thyroid Cancer
by Elisabetta Macerola, Anello Marcello Poma, Paola Vignali, Alessio Basolo, Clara Ugolini, Liborio Torregrossa, Ferruccio Santini and Fulvio Basolo
Cancers 2021, 13(5), 1139; https://doi.org/10.3390/cancers13051139 - 07 Mar 2021
Cited by 28 | Viewed by 5312
Abstract
Thyroid cancer is the most common type of endocrine-related malignancy, whose incidence rates have increased dramatically in the last few decades. Neoplasms of follicular origin generally have excellent prognosis, with the exception of less differentiated tumors. Follicular-derived thyroid cancer can manifest as a [...] Read more.
Thyroid cancer is the most common type of endocrine-related malignancy, whose incidence rates have increased dramatically in the last few decades. Neoplasms of follicular origin generally have excellent prognosis, with the exception of less differentiated tumors. Follicular-derived thyroid cancer can manifest as a variety of morphologically distinct entities, characterized by various degrees of differentiation and invasiveness. Histological evaluation is thus crucial for the definition of patients’ prognosis. However, within each histological subtype, tumor behavior can be highly variable, and, in this respect, molecular characterization can provide insightful information to refine the risk stratification of tumors. In addition to the importance of its prognostic role, molecular testing can be used to support the differential diagnosis of thyroid nodules in the absence of marked cyto-morphological aberrations. Finally, with the advent of targeted drugs, the presence of molecular alterations will guide the therapeutic strategies for patients with advanced tumors who do not respond to standard treatment. This review aims to describe the genetic landscape of follicular-derived thyroid tumors also highlighting differences across histological subtypes. Full article
(This article belongs to the Special Issue Experimental and Clinical Advances in Counteracting Progression of Solid Cancers)
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23 pages, 4571 KiB  
Review
Exosomes and Cell Communication: From Tumour-Derived Exosomes and Their Role in Tumour Progression to the Use of Exosomal Cargo for Cancer Treatment
by Andrea Nicolini, Paola Ferrari and Pier Mario Biava
Cancers 2021, 13(4), 822; https://doi.org/10.3390/cancers13040822 - 16 Feb 2021
Cited by 40 | Viewed by 3961
Abstract
Exosomes are nano-vesicle-shaped particles secreted by various cells, including cancer cells. Recently, the interest in exosomes among cancer researchers has grown enormously for their many potential roles, and many studies have focused on the bioactive molecules that they export as exosomal cargo. These [...] Read more.
Exosomes are nano-vesicle-shaped particles secreted by various cells, including cancer cells. Recently, the interest in exosomes among cancer researchers has grown enormously for their many potential roles, and many studies have focused on the bioactive molecules that they export as exosomal cargo. These molecules can function as biomarkers in diagnosis or play a relevant role in modulating the immune system and in promoting apoptosis, cancer development and progression. Others, considering exosomes potentially helpful for cancer treatment, have started to investigate them in experimental therapeutic trials. In this review, first, the biogenesis of exosomes and their main characteristics was briefly described. Then, the capability of tumour-derived exosomes and oncosomes in tumour microenvironments (TMEs) remodelling and pre-metastatic niche formation, as well as their interference with the immune system during cancer development, was examined. Finally, the potential role of exosomes for cancer therapy was discussed. Particularly, in addition, their use as carriers of natural substances and drugs with anticancer properties or carriers of boron neutron capture therapy (BNCT) and anticancer vaccines for immunotherapy, exosomes as biological reprogrammers of cancer cells have gained increased consensus. The principal aspects and the rationale of this intriguing therapeutic proposal are briefly considered. Full article
(This article belongs to the Special Issue Experimental and Clinical Advances in Counteracting Progression of Solid Cancers)
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Other

14 pages, 1252 KiB  
Systematic Review
The Evolving Role of Marked Lymph Node Biopsy (MLNB) and Targeted Axillary Dissection (TAD) after Neoadjuvant Chemotherapy (NACT) for Node-Positive Breast Cancer: Systematic Review and Pooled Analysis
by Parinita K. Swarnkar, Salim Tayeh, Michael J. Michell and Kefah Mokbel
Cancers 2021, 13(7), 1539; https://doi.org/10.3390/cancers13071539 - 26 Mar 2021
Cited by 39 | Viewed by 4537
Abstract
Targeted axillary dissection (TAD) is a new axillary staging technique that consists of the surgical removal of biopsy-proven positive axillary nodes, which are marked (marked lymph node biopsy (MLNB)) prior to neoadjuvant chemotherapy (NACT) in addition to the sentinel lymph node biopsy (SLNB). [...] Read more.
Targeted axillary dissection (TAD) is a new axillary staging technique that consists of the surgical removal of biopsy-proven positive axillary nodes, which are marked (marked lymph node biopsy (MLNB)) prior to neoadjuvant chemotherapy (NACT) in addition to the sentinel lymph node biopsy (SLNB). In a meta-analysis of more than 3000 patients, we previously reported a false-negative rate (FNR) of 13% using the SLNB alone in this setting. The aim of this systematic review and pooled analysis is to determine the FNR of MLNB alone and TAD (MLNB plus SLNB) compared with the gold standard of complete axillary lymph node dissection (cALND). The PubMed, Cochrane and Google Scholar databases were searched using MeSH-relevant terms and free words. A total of 9 studies of 366 patients that met the inclusion criteria evaluating the FNR of MLNB alone were included in the pooled analysis, yielding a pooled FNR of 6.28% (95% CI: 3.98–9.43). In 13 studies spanning 521 patients, the addition of SLNB to MLNB (TAD) was associated with a FNR of 5.18% (95% CI: 3.41–7.54), which was not significantly different from that of MLNB alone (p = 0.48). Data regarding the oncological safety of this approach were lacking. In a separate analysis of all published studies reporting successful identification and surgical retrieval of the MLN, we calculated a pooled success rate of 90.0% (95% CI: 85.1–95.1). The present pooled analysis demonstrates that the FNR associated with MLNB alone or combined with SLNB is acceptably low and both approaches are highly accurate in staging the axilla in patients with node-positive breast cancer after NACT. The SLNB adds minimal new information and therefore can be safely omitted from TAD. Further research to confirm the oncological safety of this de-escalation approach of axillary surgery is required. MLNB alone and TAD are associated with acceptably low FNRs and represent valid alternatives to cALND in patients with node-positive breast cancer after excellent response to NACT. Full article
(This article belongs to the Special Issue Experimental and Clinical Advances in Counteracting Progression of Solid Cancers)
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