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Advances in Therapeutic Strategies and Precision Medicine in Solid Tumors and Metastasis

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (31 March 2024) | Viewed by 5468

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Special Issue Editors

Dr. Silvia Di Agostino

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Guest Editor

IRCCS Regina Elena National Cancer Institute, Roma, Italy
Interests: genomic instability; cell cycle checkpoints; dna repair; transcriptional regulation; molecular oncology; head and neck; p53 family; mutant p53; hippo pathway
Special Issues, Collections and Topics in MDPI journals

Dr. Giulia Fontemaggi

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Guest Editor

Regina Elena National Cancer Institute (IRCCS), Rome, Italy
Interests: microRNAs; lncRNAs; circRNA; tumor angiogenesis; tumor-associated macrophages; cancer biology; p53
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue of Biomedicines is dedicated to the most novel therapeutic strategies for the treatment of solid tumors.

Understanding molecular cancer pathogenesis has allowed scientists to develop increasingly effective treatment strategies. Over the past decade, whole-genome DNA sequencing technologies such as next-generation sequencing (NGS) have improved the genomic knowledge of several syndromes and diseases, including cancer. Furthermore, a multi-omic approach that also considers the analysis of transcriptome, proteome, metabolome and the epigenetic DNA modifications is to be strongly pursued, to better stratify patients and provide further details on deregulated molecular pathways in tumors. Patients with a diagnosis of poor outcome due to multiple mechanisms driving therapeutic resistance could also benefit from this multi-omic approach.

For some tumors, the use of personalized medicine throughout treatment with monoclonal antibodies, immunotherapy, and epigenetic drugs has already become a reality. In the future, the main objective will be to extend the possible molecular targets to make even tumors with a high incidence of metastasis and mortality more approachable with individualized anticancer therapies.

With this ambitious goal, we aim to collect in this Special Issue original research articles and reviews highlighting recent breakthroughs in personalized medicine and novel hypothetical targetable molecular mechanisms in the field of cancer. We welcome contributions assessing topics with robust molecular rationale in precision molecular therapy, nanodrug and molecule delivery, non-coding RNA-based therapeutics, as well as novel biomarkers useful in early diagnosis and prognosis.

Dr. Silvia Di Agostino
Dr. Giulia Fontemaggi
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. Biomedicines is an international peer-reviewed open access monthly 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 2600 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

kinase inhibitor
immunotherapy
chemotherapy
precision molecular therapy
biomarkers
synthetic lethality
theranostics
drug repurposing
radiomic

Published Papers (4 papers)

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Research

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17 pages, 3024 KiB

Open AccessArticle

TCR-Engineered Lymphocytes Targeting NY-ESO-1: In Vitro Assessment of Cytotoxicity against Tumors

by Alaa Alsalloum, Saleh Alrhmoun, Julia Shevchenko, Marina Fisher, Julia Philippova, Roman Perik-Zavodskii, Olga Perik-Zavodskaia, Julia Lopatnikova, Vasily Kurilin, Marina Volynets, Yasushi Akahori, Hiroshi Shiku, Alexander Silkov and Sergey Sennikov

Biomedicines 2023, 11(10), 2805; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11102805 - 16 Oct 2023

Viewed by 1367

Abstract

Adoptive T-cell therapies tailored for the treatment of solid tumors encounter intricate challenges, necessitating the meticulous selection of specific target antigens and the engineering of highly specific T-cell receptors (TCRs). This study delves into the cytotoxicity and functional characteristics of in vitro-cultured T-lymphocytes, equipped with a TCR designed to precisely target the cancer-testis antigen NY-ESO-1. Flow cytometry analysis unveiled a notable increase in the population of cells expressing activation markers upon encountering the NY-ESO-1-positive tumor cell line, SK-Mel-37. Employing the NanoString platform, immune transcriptome profiling revealed the upregulation of genes enriched in Gene Ontology Biological Processes associated with the IFN-γ signaling pathway, regulation of T-cell activation, and proliferation. Furthermore, the modified T cells exhibited robust cytotoxicity in an antigen-dependent manner, as confirmed by the LDH assay results. Multiplex immunoassays, including LEGENDplex™, additionally demonstrated the elevated production of cytotoxicity-associated cytokines driven by granzymes and soluble Fas ligand (sFasL). Our findings underscore the specific targeting potential of engineered TCR T cells against NY-ESO-1-positive tumors. Further comprehensive in vivo investigations are essential to thoroughly validate these results and effectively harness the intrinsic potential of genetically engineered T cells for combating cancer. Full article

(This article belongs to the Special Issue Advances in Therapeutic Strategies and Precision Medicine in Solid Tumors and Metastasis)

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16 pages, 2064 KiB

Open AccessArticle

The Impact of Clinical and Histopathological Factors on Disease Progression and Survival in Thick Cutaneous Melanomas

by Dana Antonia Țăpoi, Diana Derewicz, Ancuța-Augustina Gheorghișan-Gălățeanu, Adrian Vasile Dumitru, Ana Maria Ciongariu and Mariana Costache

Biomedicines 2023, 11(10), 2616; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11102616 - 23 Sep 2023

Cited by 3 | Viewed by 921

Abstract

Thick cutaneous melanomas (Breslow depth > 4 mm) are locally advanced tumors, generally associated with poor prognosis. Nevertheless, these tumors sometimes display unpredictable behavior. This study aims to analyze clinical and histopathological features that can influence the prognosis of thick melanomas. This is a retrospective study on 94 thick primary cutaneous melanomas diagnosed between 2012 and 2018 that were followed-up for at least five years to assess disease progression and survival. We evaluated the age, gender, tumor location, histological subtype, Breslow depth, Clark level, resection margins, mitotic index, the presence/absence of ulceration, necrosis, regression, microsatellites, neurotropism, lymphovascular invasion, and the pattern of tumor-infiltrating lymphocytes, and their association with disease progression and survival. By conducting univariate analysis, we found that progression-free survival (PFS) was significantly associated with female gender, the superficial spreading melanoma (SSM) subtype, mitotic index, necrosis, microsatellites, and perineural invasion. Overall survival (OS) was significantly associated with female gender, Breslow depth, SSM subtype, necrosis, microsatellites, and perineural invasion. Through multivariate Cox proportional hazards regression, we found that the only factors associated with PFS were Breslow depth, necrosis, microsatellites, and perineural invasion, while the factors associated with OS were Breslow depth, necrosis, microsatellites, and perineural invasion. Certain histopathological features such as Breslow depth, necrosis, microsatellites, and perineural invasion could explain differences in disease evolution. This is one of the first studies to demonstrate an association between necrosis and perineural invasion and outcomes in patients with thick melanomas. By identifying high-risk patients, personalized therapy can be provided for improved prognosis. Full article

(This article belongs to the Special Issue Advances in Therapeutic Strategies and Precision Medicine in Solid Tumors and Metastasis)

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13 pages, 18319 KiB

Open AccessArticle

Usefulness of COL11A1 as a Prognostic Marker of Tumor Infiltration

by Javier Freire, Pilar García-Berbel, Belén Caramelo, Lucía García-Berbel, Victor J. Ovejero, Nuria Cadenas, Ainara Azueta and Javier Gómez-Román

Biomedicines 2023, 11(9), 2496; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11092496 - 08 Sep 2023

Viewed by 1104

Abstract

Background: Determining the infiltration of carcinomas is essential for the proper follow-up and treatment of cancer patients. However, it continues to be a diagnostic challenge for pathologists in multiple types of tumors. In previous studies (carried out in surgical specimens), the protein COL11A1 has been postulated as an infiltration marker mainly expressed in the extracellular matrix (ECM). We hypothesized that a differential expression of COL11A1 may exist in the peritumoral stroma of tumors that have acquired infiltrating properties and that it may be detected in the small biopsies usually available in normal clinical practice. Material and methods: In our study, we performed immunohistochemical staining in more than 350 invasive and noninvasive small samples obtained via core needle biopsy (CNB), colonoscopy, or transurethral resection of bladder tumor (TURBT) of breast, colorectal, bladder, and ovarian cancer. Results: Our results revealed that COL11A1 immunostaining had a sensitivity to classify the samples into infiltrative vs. noninfiltrative tumors of 94% (breast), 97% (colorectal), >90% (bladder), and 74% (ovarian); and a specificity of 97% (breast), 100% (colorectal), and >90% (bladder). In ovarian cancer, the negative predictive value (0.59) did not present improvement over the usual histopathological markers. In all samples tested, the cumulative sensitivity was 86% and the specificity 96% (p < 0.0001). Conclusions: COL11A1-positive immunostaining in small biopsies of breast, colon, bladder and ovarian cancer is an accurate predictive marker of tumor infiltration that can be easily implemented in daily clinical practice. Full article

(This article belongs to the Special Issue Advances in Therapeutic Strategies and Precision Medicine in Solid Tumors and Metastasis)

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Review

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17 pages, 625 KiB

Open AccessReview

New Therapeutic Perspectives in Prostate Cancer: Patient-Derived Organoids and Patient-Derived Xenograft Models in Precision Medicine

by Vittoria Rago, Anna Perri and Silvia Di Agostino

Biomedicines 2023, 11(10), 2743; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11102743 - 10 Oct 2023

Cited by 1 | Viewed by 1323

Abstract

One of the major goals in the advancement of basic cancer research focuses on the development of new anticancer therapies. To understand the molecular mechanisms of cancer progression, acquired drug resistance, and the metastatic process, the use of preclinical in vitro models that faithfully summarize the properties of the tumor in patients is still a necessity. The tumor is represented by a diverse group of cell clones, and in recent years, to reproduce in vitro preclinical tumor models, monolayer cell cultures have been supplanted by patient-derived xenograft (PDX) models and cultured organoids derived from the patient (PDO). These models have proved indispensable for the study of the tumor microenvironment (TME) and its interaction with tumor cells. Prostate cancer (PCa) is the most common neoplasia in men in the world. It is characterized by genomic instability and resistance to conventional therapies. Despite recent advances in diagnosis and treatment, PCa remains a leading cause of cancer death. Here, we review the studies of the last 10 years as the number of papers is growing very fast in the field. We also discuss the discovered limitations and the new challenges in using the organoid culture system and in using PDXs in studying the prostate cancer phenotype, performing drug testing, and developing anticancer molecular therapies. Full article

(This article belongs to the Special Issue Advances in Therapeutic Strategies and Precision Medicine in Solid Tumors and Metastasis)

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