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State-of-the-Art Molecular Oncology in Italy

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 28027

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Special Issue Editors

Dr. Carmine Stolfi

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Collection Editor

Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy
Interests: colorectal cancer; immunotherapy; inflammatory bowel diseases; anti-cancer drugs
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Dr. Federica Laudisi

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Collection Editor

Department of Systems Medicine, University of Rome “Tor Vergata”, Rome, Italy
Interests: inflammatory bowel disease; intestinal inflammation; colorectal cancer; intestinal epithelial barrier; microbiota; inflammasome
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Prof. Dr. Federico Cappuzzo

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Collection Editor

Department of Oncology-Hematology, AUSL della Romagna, Ravenna, Italy
Interests: lung cancer; molecular oncology; targeted therapy; immunotherapy
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Dr. Elena Lastraioli

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Collection Editor

Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence, Viale GB Morgagni, 50134 Firenze, Italy
Interests: cancer; molecular biology; genetics; histology; Liquid Biopsy; ion channels
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Special Issue Information

Dear Colleagues,

Through the use of diverse techniques and cutting edge technologies, molecular oncology aims to investigate and characterize the molecular changes that underpin the pathogenesis and progression of malignant diseases, with the ultimate goal to improve prevention strategies and treatment options for cancer patients.

An increasing number of research teams in Italy have been devoting considerable effort to developing and studying molecular oncology, significantly consolidating our understanding of this field. By collecting high-quality contributions from scholars working in Italian universities and research institutes, this Special Issue aims to provide a comprehensive overview of the latest advances and the most recent discoveries and progress in all fields of molecular oncology in Italy.

We encourage submission of original full research papers as well as review articles dealing with novel mechanistic insights and details of the molecular signatures of oncogenic transformation. We also encourage submission of manuscripts that focus on translating basic molecular knowledge to new medical applications in oncology. Articles reporting novel technologies aimed at identifying disease biomarkers are also welcomed.

Topics include, but are not limited to, the following:

New insights in the molecular mechanisms of cancer growth, invasion and metastasis
Cancer emerging technologies (e.g., bioinformatics, proteomics, metabolomics, tissue arrays, imaging)
New molecular biomarkers and profiling of cancers: diagnosis, prognosis, stratification and efficacy
Molecular interactions in the tumor microenvironment, including tumor-immune cell, tumor-stroma and tumor-microbiota interactions
Genomic profiling of human cancers, including genetics, epigenetics, and genomic instability
Preclinical research that leads to novel therapies derived from molecular processes and cellular interactions, including gene therapy, nanomedicine-based therapies, therapy based on biologicals, cancer vaccines and other types of immunotherapies (e.g., oncolytic viruses, CAR T cells)

Dr. Carmine Stolfi
Dr. Federica Laudisi
Prof. Dr. Federico Cappuzzo
Dr. Elena Lastraioli
Collection 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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

cancer
Italy
tumor microenvironment
inflammation
cytokines
metastasis
angiogenesis
biomarkers
apoptosis
cell cycle
preclinical models
immunotherapy
nanomedicine
vaccine
gene therapy
bioinformatics
OMICS
genetics

Published Papers (13 papers)

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Editorial

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6 pages, 210 KiB

Open AccessEditorial

Advances in Immunotherapy and Innovative Therapeutic Approaches for Cancer Treatment: Editorial to the Special Issue “State-of-the-Art Molecular Oncology in Italy”

by Federica Laudisi and Carmine Stolfi

Int. J. Mol. Sci. 2023, 24(10), 8929; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24108929 - 18 May 2023

Viewed by 828

Abstract

Cancer remains one of the most common causes of death worldwide, mainly due to late diagnosis and the lack of efficient therapeutic options for patients with advanced diseases [...] Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Italy)

Research

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20 pages, 7043 KiB

Open AccessArticle

Insights into the Peritumoural Brain Zone of Glioblastoma: CDK4 and EXT2 May Be Potential Drivers of Malignancy

by Martina Giambra, Andrea Di Cristofori, Donatella Conconi, Matilde Marzorati, Serena Redaelli, Melissa Zambuto, Alessandra Rocca, Louis Roumy, Giorgio Carrabba, Marialuisa Lavitrano, Gaia Roversi, Carlo Giussani and Angela Bentivegna

Int. J. Mol. Sci. 2023, 24(3), 2835; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24032835 - 02 Feb 2023

Cited by 5 | Viewed by 2082

Abstract

Despite the efforts made in recent decades, glioblastoma is still the deadliest primary brain cancer without cure. The potential role in tumour maintenance and progression of the peritumoural brain zone (PBZ), the apparently normal area surrounding the tumour, has emerged. Little is known about this area due to a lack of common definition and due to difficult sampling related to the functional role of peritumoural healthy brain. The aim of this work was to better characterize the PBZ and to identify genes that may have role in its malignant transformation. Starting from our previous study on the comparison of the genomic profiles of matched tumour core and PBZ biopsies, we selected CDK4 and EXT2 as putative malignant drivers of PBZ. The gene expression analysis confirmed their over-expression in PBZ, similarly to what happens in low-grade glioma and glioblastoma, and CDK4 high levels seem to negatively influence patient overall survival. The prognostic role of CDK4 and EXT2 was further confirmed by analysing the TCGA cohort and bioinformatics prediction on their gene networks and protein–protein interactions. These preliminary data constitute a good premise for future investigations on the possible role of CDK4 and EXT2 in the malignant transformation of PBZ. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Italy)

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12 pages, 848 KiB

Open AccessArticle

Clinical Significance of Molecular Subtypes in Western Advanced Gastric Cancer: A Real-World Multicenter Experience

by Massimiliano Salati, Michele Ghidini, Matteo Paccagnella, Luca Reggiani Bonetti, Alessandro Bocconi, Andrea Spallanzani, Fabio Gelsomino, Francesca Barbin, Ornella Garrone, Bruno Daniele, Massimo Dominici, Antonio Facciorusso and Angelica Petrillo

Int. J. Mol. Sci. 2023, 24(1), 813; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24010813 - 03 Jan 2023

Cited by 5 | Viewed by 2195

Abstract

In recent years, the molecular subtyping of gastric cancer has led to the identification of novel clinically relevant biomarkers as well as promising therapeutic targets. In parallel, the advent of checkpoint inhibitors has expanded treatment options beyond conventional chemotherapy. Compelling evidence has shown unprecedented efficacy results for anti-PD1-based therapies in the molecular subgroups of dMMR/MSI-h, EBV+ and PD-L1 CPS+ patients, to the point that these are granted approval for gastric cancer adenocarcinoma (AGC) in several countries. Despite this, cytotoxic chemotherapy remains the only treatment choice for the considerable proportion of biomarkers-negative patients. In this context, little is known about the association between subtypes-defining biomarkers (HER2, MMR/MSI, PD-L1, and EBV) and the efficacy of standard chemotherapy in non-Asian AGC. Here, we aimed to investigate the prevalence, the clinic-pathologic features, and the impact on treatment outcome of clinical molecular subtypes in a new-diagnosed Western cohort of AGC. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Italy)

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15 pages, 2422 KiB

Open AccessCommunication

Monitoring Somatic Genetic Alterations in Circulating Cell-Free DNA/RNA of Patients with “Oncogene-Addicted” Advanced Lung Adenocarcinoma: A Real-World Clinical Study

by Laura Lupini, Roberta Roncarati, Lorenzo Belluomini, Federica Lancia, Cristian Bassi, Lucilla D’Abundo, Angelo Michilli, Paola Guerriero, Alessandra Fasano, Elisa Tiberi, Andrea Salamone, Donato Michele Cosi, Elena Saccenti, Valentina Tagliatti, Iva Maestri, Silvia Sabbioni, Stefano Volinia, Roberta Gafà, Giovanni Lanza, Antonio Frassoldati and Massimo Negrini Show full author list Hide full author list

Int. J. Mol. Sci. 2022, 23(15), 8546; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158546 - 01 Aug 2022

Cited by 2 | Viewed by 1721

Abstract

Liquid biopsy has advantages over tissue biopsy, but also some technical limitations that hinder its wide use in clinical applications. In this study, we aimed to evaluate the usefulness of liquid biopsy for the clinical management of patients with advanced-stage oncogene-addicted non-small-cell lung adenocarcinomas. The investigation was conducted on a series of cases—641 plasma samples from 57 patients—collected in a prospective consecutive manner, which allowed us to assess the benefits and limitations of the approach in a real-world clinical context. Thirteen samples were collected at diagnosis, and the additional samples during the periodic follow-up visits. At diagnosis, we detected mutations in ctDNA in 10 of the 13 cases (77%). During follow-up, 36 patients progressed. In this subset of patients, molecular analyses of plasma DNA/RNA at progression revealed the appearance of mutations in 29 patients (80.6%). Mutations in ctDNA/RNA were typically detected an average of 80 days earlier than disease progression assessed by RECIST or clinical evaluations. Among the cases positive for mutations, we observed 13 de novo mutations, responsible for the development of resistance to therapy. This study allowed us to highlight the advantages and disadvantages of liquid biopsy, which led to suggesting algorithms for the use of liquid biopsy analyses at diagnosis and during monitoring of therapy response. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Italy)

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18 pages, 3119 KiB

Open AccessArticle

Evaluation of the Molecular Landscape in PD-L1 Positive Metastatic NSCLC: Data from Campania, Italy

by Pasquale Pisapia, Antonino Iaccarino, Caterina De Luca, Gennaro Acanfora, Claudio Bellevicine, Roberto Bianco, Bruno Daniele, Luisa Ciampi, Marco De Felice, Teresa Fabozzi, Luigi Formisano, Pasqualina Giordano, Cesare Gridelli, Giovanni Pietro Ianniello, Annamaria Libroia, Paolo Maione, Mariantonia Nacchio, Fabio Pagni, Giovanna Palmieri, Francesco Pepe, Gianluca Russo, Maria Salatiello, Antonio Santaniello, Rachele Scamarcio, Davide Seminati, Michele Troia, Giancarlo Troncone, Elena Vigliar and Umberto Malapelle Show full author list Hide full author list

Int. J. Mol. Sci. 2022, 23(15), 8541; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158541 - 01 Aug 2022

Cited by 3 | Viewed by 1984

Abstract

Background: Immune-checkpoint inhibitors (ICIs) have increased and improved the treatment options for patients with non-oncogene-addicted advanced stage non-small cell lung cancer (NSCLC). However, the role of ICIs in oncogene-addicted advanced stage NSCLC patients is still debated. In this study, in an attempt to fill in the informational gap on the effect of ICIs on other driver mutations, we set out to provide a molecular landscape of clinically relevant oncogenic drivers in programmed death-ligand 1 (PD-L1) positive NSCLC patients. Methods: We retrospectively reviewed data on 167 advanced stage NSCLC PD-L1 positive patients (≥1%) who were referred to our clinic for molecular evaluation of five driver oncogenes, namely, EGFR, KRAS, BRAF, ALK and ROS1. Results: Interestingly, n = 93 (55.7%) patients showed at least one genomic alteration within the tested genes. Furthermore, analyzing a subset of patients with PD-L1 tumor proportion score (TPS) ≥ 50% and concomitant gene alterations (n = 8), we found that n = 3 (37.5%) of these patients feature clinical benefit with ICIs administration, despite the presence of a concomitant KRAS gene alteration. Conclusions: In this study, we provide a molecular landscape of clinically relevant biomarkers in NSCLC PD-L1 positive patients, along with data evidencing the clinical benefit of ICIs in patient NSCLC PD-L1 positive alterations. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Italy)

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16 pages, 2070 KiB

Open AccessArticle

A Proteomic Platform Unveils the Brain Glycogen Phosphorylase as a Potential Therapeutic Target for Glioblastoma Multiforme

by Giusy Ferraro, Matteo Mozzicafreddo, Roberta Ettari, Lorenzo Corsi and Maria Chiara Monti

Int. J. Mol. Sci. 2022, 23(15), 8200; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158200 - 25 Jul 2022

Cited by 5 | Viewed by 1628

Abstract

In the last few years, several efforts have been made to identify original strategies against glioblastoma multiforme (GBM): this requires a more detailed investigation of the molecular mechanism of GBM so that novel targets can be identified for new possible therapeutic agents. Here, using a combined biochemical and proteomic approach, we evaluated the ability of a blood–brain barrier-permeable 2,3-benzodiazepin-4-one, called 1g, to interfere with the activity and the expression of brain glycogen phosphorylase (PYGB) on U87MG cell line in parallel with the capability of this compound to inhibit the cell growth and cycle. Thus, our results highlighted PYGB as a potential therapeutic target in GBM prompting 1g as a capable anticancer drug thanks to its ability to negatively modulate the uptake and metabolism of glucose, the so-called “Warburg effect”, whose increase is considered a common feature of cancer cells in respect of their normal counterparts. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Italy)

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20 pages, 4996 KiB

Open AccessArticle

The Transcriptional Landscape of BRAF Wild Type Metastatic Melanoma: A Pilot Study

by Elena Lastraioli, Federico Alessandro Ruffinatti, Giacomo Bagni, Luca Visentin, Francesco di Costanzo, Luca Munaron and Annarosa Arcangeli

Int. J. Mol. Sci. 2022, 23(13), 6898; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23136898 - 21 Jun 2022

Cited by 3 | Viewed by 1647

Abstract

Melanoma is a relatively rare disease worldwide; nevertheless, it has a great relevance in some countries, such as in Europe. In order to shed some light upon the transcriptional profile of skin melanoma, we compared the gene expression of six independent tumours (all progressed towards metastatic disease and with wild type BRAF) to the expression profile of non-dysplastic melanocytes (considered as a healthy control) in a pilot study. Paraffin-embedded samples were manually micro-dissected to obtain enriched samples, and then, RNA was extracted and analysed through a microarray-based approach. An exhaustive bioinformatics analysis was performed to identify differentially expressed transcripts between the two groups, as well as enriched functional terms. Overall, 50 up- and 19 downregulated transcripts were found to be significantly changed in the tumour compared to the control tissue. Among the upregulated transcripts, the majority belonged to the immune response group and to the proteasome, while most of the downregulated genes were related to cytosolic ribosomes. A Gene Set Enrichment Analysis (GSEA), along with the RNA-Seq data retrieved from the TCGA/GTEx databases, confirmed the general trend of downregulation affecting cytoribosome proteins. In contrast, transcripts coding for mitoribosome proteins showed the opposite trend. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Italy)

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Review

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13 pages, 581 KiB

Open AccessReview

Anthelmintic Drugs as Emerging Immune Modulators in Cancer

by Carmine Stolfi, Teresa Pacifico, Anderson Luiz-Ferreira, Giovanni Monteleone and Federica Laudisi

Int. J. Mol. Sci. 2023, 24(7), 6446; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24076446 - 29 Mar 2023

Cited by 3 | Viewed by 3419

Abstract

Despite recent advances in treatment approaches, cancer is still one of the leading causes of death worldwide. Restoration of tumor immune surveillance represents a valid strategy to overcome the acquired resistance and cytotoxicity of conventional therapies in oncology and immunotherapeutic drugs, such as immune checkpoint inhibitors and immunogenic cell death inducers, and has substantially progressed the treatment of several malignancies and improved the clinical management of advanced disease. Unfortunately, because of tumor-intrinsic and/or -extrinsic mechanisms for escaping immune surveillance, only a fraction of patients clinically respond to and benefit from cancer immunotherapy. Accumulating evidence derived from studies of drug repositioning, that is, the strategy to identify new uses for approved or investigational drugs that are outside the scope of the original medical indication, has suggested that some anthelmintic drugs, in addition to their antineoplastic effects, exert important immunomodulatory actions on specific subsets of immune cell and related pathways. In this review, we report and discuss current knowledge on the impact of anthelmintic drugs on host immunity and their potential implication in cancer immunotherapy. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Italy)

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24 pages, 1205 KiB

Open AccessReview

Programmed Cell Death-Ligand 1 in Head and Neck Squamous Cell Carcinoma: Molecular Insights, Preclinical and Clinical Data, and Therapies

by Piero Giuseppe Meliante, Christian Barbato, Federica Zoccali, Massimo Ralli, Antonio Greco, Marco de Vincentiis, Andrea Colizza, Carla Petrella, Giampiero Ferraguti, Antonio Minni and Marco Fiore

Int. J. Mol. Sci. 2022, 23(23), 15384; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232315384 - 06 Dec 2022

Cited by 13 | Viewed by 2328

Abstract

Aberrant expression of the programmed cell death protein ligand 1 (PD-L1) constitutes one of the main immune evasion mechanisms of cancer cells. The approval of drugs against the PD-1-PD-L1 axis has given new impetus to the chemo-therapy of many malignancies. We performed a literature review from 1992 to August 2022, summarizing evidence regarding molecular structures, physiological and pathological roles, mechanisms of PD-L1 overexpression, and immunotherapy evasion. Furthermore, we summarized the studies concerning head and neck squamous cell carcinomas (HNSCC) immunotherapy and the prospects for improving the associated outcomes, such as identifying treatment response biomarkers, new pharmacological combinations, and new molecules. PD-L1 overexpression can occur via four mechanisms: genetic modifications; inflammatory signaling; oncogenic pathways; microRNA or protein-level regulation. Four molecular mechanisms of resistance to immunotherapy have been identified: tumor cell adaptation; changes in T-cell function or proliferation; alterations of the tumor microenvironment; alternative immunological checkpoints. Immunotherapy was indeed shown to be superior to traditional chemotherapy in locally advanced/recurrent/metastatic HNSCC treatments. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Italy)

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13 pages, 910 KiB

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Unraveling Mitochondrial Determinants of Tumor Response to Radiation Therapy

by Mattia Zaffaroni, Maria Giulia Vincini, Giulia Corrao, Giulia Marvaso, Matteo Pepa, Giuseppe Viglietto, Nicola Amodio and Barbara Alicja Jereczek-Fossa

Int. J. Mol. Sci. 2022, 23(19), 11343; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231911343 - 26 Sep 2022

Cited by 4 | Viewed by 1614

Abstract

Radiotherapy represents a highly targeted and efficient treatment choice in many cancer types, both with curative and palliative intents. Nevertheless, radioresistance, consisting in the adaptive response of the tumor to radiation-induced damage, represents a major clinical problem. A growing body of the literature suggests that mechanisms related to mitochondrial changes and metabolic remodeling might play a major role in radioresistance development. In this work, the main contributors to the acquired cellular radioresistance and their relation with mitochondrial changes in terms of reactive oxygen species, hypoxia, and epigenetic alterations have been discussed. We focused on recent findings pointing to a major role of mitochondria in response to radiotherapy, along with their implication in the mechanisms underlying radioresistance and radiosensitivity, and briefly summarized some of the recently proposed mitochondria-targeting strategies to overcome the radioresistant phenotype in cancer. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Italy)

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12 pages, 3828 KiB

Open AccessReview

Nanotechnology Meets Oncology: A Perspective on the Role of the Personalized Nanoparticle-Protein Corona in the Development of Technologies for Pancreatic Cancer Detection

by Damiano Caputo, Erica Quagliarini, Daniela Pozzi and Giulio Caracciolo

Int. J. Mol. Sci. 2022, 23(18), 10591; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231810591 - 13 Sep 2022

Cited by 5 | Viewed by 2048

Abstract

In recent years nanotechnology has opened exciting opportunities in the struggle against cancer. In 2007 Dawson and coworkers demonstrated that nanomaterials exposed to biological fluids are coated with plasma proteins that form the so-called “protein corona”. A few years later our joint research team made of physicists, chemists, biotechnologists, surgeons, oncologists, and bioinformaticians introduced the concept of “personalized protein corona” and demonstrated that it is unique for each human condition. This concept paved the way for the development of nano-enabled blood (NEB) tests for the diagnosis of pancreatic ductal adenocarcinoma (PDAC). These studies gave an impetus to serious work in the field that came to maturity in the late 2010s. In this special issue, we provide the reader with a comprehensive overview of the most significant discoveries of our research team in the field of PDAC detection. We focus on the main achievements with an emphasis on the fundamental aspects of this arena and how they shaped the integration of different scientific backgrounds towards the development of advanced diagnostic technologies. We conclude the review by outlining future perspectives and opportunities to transform the NEB tests into a reliable clinical diagnostic technology for early diagnosis, follow-up, and management of PDAC patients. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Italy)

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23 pages, 2381 KiB

Open AccessReview

The Proteoglycan Glypican-1 as a Possible Candidate for Innovative Targeted Therapeutic Strategies for Pancreatic Ductal Adenocarcinoma

by Davide Busato, Monica Mossenta, Michele Dal Bo, Paolo Macor and Giuseppe Toffoli

Int. J. Mol. Sci. 2022, 23(18), 10279; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231810279 - 07 Sep 2022

Cited by 3 | Viewed by 2118

Abstract

Pancreatic ductal adenocarcinoma (PDAC) accounts for 90% of all pancreatic cancers, with a 5-year survival rate of 7% and 80% of patients diagnosed with advanced or metastatic malignancies. Despite recent advances in diagnostic testing, surgical techniques, and systemic therapies, there remain limited options for the effective treatment of PDAC. There is an urgent need to develop targeted therapies that are able to differentiate between cancerous and non-cancerous cells to reduce side effects and better inhibit tumor growth. Antibody-targeted strategies are a potentially effective option for introducing innovative therapies. Antibody-based immunotherapies and antibody-conjugated nanoparticle-based targeted therapies with antibodies targeting specific tumor-associated antigens (TAA) can be proposed. In this context, glypican-1 (GPC1), which is highly expressed in PDAC and not expressed or expressed at very low levels in non-malignant lesions and healthy pancreatic tissues, is a useful TAA that can be achieved by a specific antibody-based immunotherapy and antibody-conjugated nanoparticle-based targeted therapy. In this review, we describe the main clinical features of PDAC. We propose the proteoglycan GPC1 as a useful TAA for PDAC-targeted therapies. We also provide a digression on the main developed approaches of antibody-based immunotherapy and antibody-conjugated nanoparticle-based targeted therapy, which can be used to target GPC1. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Italy)

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27 pages, 1607 KiB

Open AccessReview

Novel Nanotechnology Approaches to Overcome Drug Resistance in the Treatment of Hepatocellular Carcinoma: Glypican 3 as a Useful Target for Innovative Therapies

by Monica Mossenta, Davide Busato, Michele Dal Bo, Paolo Macor and Giuseppe Toffoli

Int. J. Mol. Sci. 2022, 23(17), 10038; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231710038 - 02 Sep 2022

Cited by 4 | Viewed by 2838

Abstract

Hepatocellular carcinoma (HCC) is the second most lethal tumor, with a 5-year survival rate of 18%. Early stage HCC is potentially treatable by therapies with curative intent, whereas chemoembolization/radioembolization and systemic therapies are the only therapeutic options for intermediate or advanced HCC. Drug resistance is a critical obstacle in the treatment of HCC that could be overcome by the use of targeted nanoparticle-based therapies directed towards specific tumor-associated antigens (TAAs) to improve drug delivery. Glypican 3 (GPC3) is a member of the glypican family, heparan sulfate proteoglycans bound to the cell surface via a glycosylphosphatidylinositol anchor. The high levels of GPC3 detected in HCC and the absence or very low levels in normal and non-malignant liver make GPC3 a promising TAA candidate for targeted nanoparticle-based therapies. The use of nanoparticles conjugated with anti-GPC3 agents may improve drug delivery, leading to a reduction in severe side effects caused by chemotherapy and increased drug release at the tumor site. In this review, we describe the main clinical features of HCC and the common treatment approaches. We propose the proteoglycan GPC3 as a useful TAA for targeted therapies. Finally, we describe nanotechnology approaches for anti-GPC3 drug delivery systems based on NPs for HCC treatment. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Italy)

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