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Article ; Online: Subtype Transdifferentiation in Human Cancer: The Power of Tissue Plasticity in Tumor Progression.

Fedele, Monica / Cerchia, Laura / Battista, Sabrina

2024 Volume 13, Issue 4

Abstract: The classification of tumors into subtypes, characterized by phenotypes determined by specific differentiation pathways, aids diagnosis and directs therapy towards targeted approaches. However, with the advent and explosion of next-generation sequencing, ...

Abstract	The classification of tumors into subtypes, characterized by phenotypes determined by specific differentiation pathways, aids diagnosis and directs therapy towards targeted approaches. However, with the advent and explosion of next-generation sequencing, cancer phenotypes are turning out to be far more heterogenous than initially thought, and the classification is continually being updated to include more subtypes. Tumors are indeed highly dynamic, and they can evolve and undergo various changes in their characteristics during disease progression. The picture becomes even more complex when the tumor responds to a therapy. In all these cases, cancer cells acquire the ability to transdifferentiate, changing subtype, and adapt to changing microenvironments. These modifications affect the tumor's growth rate, invasiveness, response to treatment, and overall clinical behavior. Studying tumor subtype transitions is crucial for understanding tumor evolution, predicting disease outcomes, and developing personalized treatment strategies. We discuss this emerging hallmark of cancer and the molecular mechanisms involved at the crossroads between tumor cells and their microenvironment, focusing on four different human cancers in which tissue plasticity causes a subtype switch: breast cancer, prostate cancer, glioblastoma, and pancreatic adenocarcinoma.
MeSH term(s)	Male ; Humans ; Cell Transdifferentiation ; Adenocarcinoma ; Pancreatic Neoplasms ; Neoplastic Processes ; Breast Neoplasms/pathology ; Tumor Microenvironment/genetics
Language	English
Publishing date	2024-02-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells13040350
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Aptamers: Promising Tools for Cancer Diagnosis and Therapy.

Cerchia, Laura

Cancers

2018 Volume 10, Issue 5

Abstract: The most common approaches to cancer treatment have been, for decades, based on surgical excision, radio- and/or chemotherapy, which, in spite of their modest survival benefits, still encounter several limitations, in part due to their lack of ... ...

Abstract	The most common approaches to cancer treatment have been, for decades, based on surgical excision, radio- and/or chemotherapy, which, in spite of their modest survival benefits, still encounter several limitations, in part due to their lack of specificity.[...].
Language	English
Publishing date	2018-05-03
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers10050132
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Article ; Online: Identification of selective 5-LOX and FLAP inhibitors as novel anti-inflammatory agents by ligand-based virtual screening.

Cerchia, Carmen / Küfner, Laura / Werz, Oliver / Lavecchia, Antonio

European journal of medicinal chemistry

2023 Volume 263, Page(s) 115932

Abstract: Inflammation is a multifaceted biological process in which the conversion of arachidonic acid to eicosanoids, including prostaglandins and leukotrienes (LTs), plays a crucial role. 5-Lipoxygenase (5-LOX) is a key enzyme in cellular LT biosynthesis, and ... ...

Abstract	Inflammation is a multifaceted biological process in which the conversion of arachidonic acid to eicosanoids, including prostaglandins and leukotrienes (LTs), plays a crucial role. 5-Lipoxygenase (5-LOX) is a key enzyme in cellular LT biosynthesis, and it is supported by the accessory protein 5-lipoxygenase-activating protein (FLAP). Pharmacological interventions to modulate LTs aim at either decreasing their biosynthesis or at mitigating their biological effects. Therefore, inhibiting 5-LOX or FLAP represents a useful strategy to reduce inflammation. Herein we present the identification and pharmacological evaluation of novel inhibitors targeting 5-LOX or FLAP. By means of a ligand-based virtual screening approach, we selected 38 compounds for in vitro assays. Among them, ALR-38 exhibits direct 5-LOX inhibition, while ALR-6 and ALR-27 showed potential as FLAP inhibitors. These latter not only reduced LT production but also promoted the generation of specialized pro-resolving mediators in specific human macrophage phenotypes. Interestingly, the identified compounds turned out to be selective for their respective targets, as none of them displayed activity towards microsomal prostaglandin E
MeSH term(s)	Humans ; 5-Lipoxygenase-Activating Protein Inhibitors/pharmacology ; Ligands ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; Inflammation/drug therapy ; Inflammation/metabolism ; Leukotrienes/metabolism ; Arachidonate 5-Lipoxygenase/metabolism ; Lipoxygenase Inhibitors/pharmacology ; Lipoxygenase Inhibitors/therapeutic use
Chemical Substances	5-Lipoxygenase-Activating Protein Inhibitors ; Ligands ; Anti-Inflammatory Agents ; Leukotrienes ; Arachidonate 5-Lipoxygenase (EC 1.13.11.34) ; Lipoxygenase Inhibitors
Language	English
Publishing date	2023-11-08
Publishing country	France
Document type	Journal Article
ZDB-ID	188597-2
ISSN	1768-3254 ; 0009-4374 ; 0223-5234
ISSN (online)	1768-3254
ISSN	0009-4374 ; 0223-5234
DOI	10.1016/j.ejmech.2023.115932
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Article ; Online: Mechanism of Action of Lactic Acid on Histones in Cancer.

Sgarra, Riccardo / Battista, Sabrina / Cerchia, Laura / Manfioletti, Guidalberto / Fedele, Monica

Antioxidants & redox signaling

2023 Volume 40, Issue 4-6, Page(s) 236–249

Abstract: Significance: ...

Abstract	Significance:
MeSH term(s)	Humans ; Histones/metabolism ; Lactic Acid ; Chromatin ; Epigenesis, Genetic ; Neoplasms/drug therapy ; Neoplasms/genetics ; Tumor Microenvironment
Chemical Substances	Histones ; Lactic Acid (33X04XA5AT) ; Chromatin
Language	English
Publishing date	2023-04-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1483836-9
ISSN	1557-7716 ; 1523-0864
ISSN (online)	1557-7716
ISSN	1523-0864
DOI	10.1089/ars.2022.0190
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Article: Aptamer-Based Strategies to Boost Immunotherapy in TNBC.

Agnello, Lisa / d'Argenio, Annachiara / Nilo, Roberto / Fedele, Monica / Camorani, Simona / Cerchia, Laura

Cancers

2023 Volume 15, Issue 7

Abstract: The immune system (IS) may play a crucial role in preventing tumor development and progression, leading, over the last years, to the development of effective cancer immunotherapies. Nevertheless, immune evasion, the capability of tumors to circumvent ... ...

Abstract	The immune system (IS) may play a crucial role in preventing tumor development and progression, leading, over the last years, to the development of effective cancer immunotherapies. Nevertheless, immune evasion, the capability of tumors to circumvent destructive host immunity, remains one of the main obstacles to overcome for maximizing treatment success. In this context, promising strategies aimed at reshaping the tumor immune microenvironment and promoting antitumor immunity are rapidly emerging. Triple-negative breast cancer (TNBC), an aggressive breast cancer subtype with poor outcomes, is highly immunogenic, suggesting immunotherapy is a viable strategy. As evidence of this, already, two immunotherapies have recently become the standard of care for patients with PD-L1 expressing tumors, which, however, represent a low percentage of patients, making more active immunotherapeutic approaches necessary. Aptamers are short, highly structured, single-stranded oligonucleotides that bind to their protein targets at high affinity and specificity. They are used for therapeutic purposes in the same way as monoclonal antibodies; thus, various aptamer-based strategies are being actively explored to stimulate the IS's response against cancer cells. The aim of this review is to discuss the potential of the recently reported aptamer-based approaches to boost the IS to fight TNBC.
Language	English
Publishing date	2023-03-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15072010
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Article ; Online: Aptamers and antibodies: rivals or allies in cancer targeted therapy?

Agnello, Lisa / Camorani, Simona / Fedele, Monica / Cerchia, Laura

Exploration of targeted anti-tumor therapy

2021 Volume 2, Issue 1, Page(s) 107–121

Abstract: The goal of an efficacious cancer therapy is to specifically target diseased cells at high accuracy while sparing normal, healthy cells. Over the past three decades, immunotherapy, based on the use of monoclonal antibodies (mAbs) directed against tumor- ... ...

Abstract	The goal of an efficacious cancer therapy is to specifically target diseased cells at high accuracy while sparing normal, healthy cells. Over the past three decades, immunotherapy, based on the use of monoclonal antibodies (mAbs) directed against tumor-associated antigens, to inhibit their oncogenic function, or against immune checkpoints, to modulate specific T cell responses against cancer, has proven to be an important strategy for cancer therapy. Nevertheless, the number of mAbs approved for clinical use is still limited because of significant drawbacks to their applicability. Oligonucleotide aptamers, similarly to antibodies, form high-affinity bonds with their specific protein targets, thus representing an effective tool for active cancer targeting. Compared to antibodies, aptamers' use as therapeutic agents benefits from their low size, low/no immunogenicity, simple synthesis and design flexibility for improving efficacy and stability. This review intends to highlight recently emerged applications of aptamers as recognition elements, from biomarker discovery to targeted drug delivery and targeted treatment, showing aptamers' potential to work in conjunction with antibodies for attacking cancer from multiple flanks.
Language	English
Publishing date	2021-02-28
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2692-3114
ISSN (online)	2692-3114
DOI	10.37349/etat.2021.00035
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Article ; Online: The Epithelial-Mesenchymal Transition at the Crossroads between Metabolism and Tumor Progression.

Fedele, Monica / Sgarra, Riccardo / Battista, Sabrina / Cerchia, Laura / Manfioletti, Guidalberto

International journal of molecular sciences

2022 Volume 23, Issue 2

Abstract: The transition between epithelial and mesenchymal phenotype is emerging as a key determinant of tumor cell invasion and metastasis. It is a plastic process in which epithelial cells first acquire the ability to invade the extracellular matrix and migrate ...

Abstract	The transition between epithelial and mesenchymal phenotype is emerging as a key determinant of tumor cell invasion and metastasis. It is a plastic process in which epithelial cells first acquire the ability to invade the extracellular matrix and migrate into the bloodstream via transdifferentiation into mesenchymal cells, a phenomenon known as epithelial-mesenchymal transition (EMT), and then reacquire the epithelial phenotype, the reverse process called mesenchymal-epithelial transition (MET), to colonize a new organ. During all metastatic stages, metabolic changes, which give cancer cells the ability to adapt to increased energy demand and to withstand a hostile new environment, are also important determinants of successful cancer progression. In this review, we describe the complex interaction between EMT and metabolism during tumor progression. First, we outline the main connections between the two processes, with particular emphasis on the role of cancer stem cells and LncRNAs. Then, we focus on some specific cancers, such as breast, lung, and thyroid cancer.
MeSH term(s)	Animals ; Biomarkers ; Biomarkers, Tumor ; Disease Management ; Disease Progression ; Disease Susceptibility ; Drug Resistance, Neoplasm ; Energy Metabolism ; Epithelial-Mesenchymal Transition/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Metabolic Networks and Pathways ; Molecular Targeted Therapy ; Neoplasms/etiology ; Neoplasms/metabolism ; Neoplasms/pathology ; Neoplasms/therapy ; Neoplastic Stem Cells/drug effects ; Neoplastic Stem Cells/metabolism ; Organ Specificity ; Oxidative Stress ; RNA Interference ; RNA, Long Noncoding/genetics ; Signal Transduction ; Transcription Factors/metabolism ; Tumor Microenvironment
Chemical Substances	Biomarkers ; Biomarkers, Tumor ; RNA, Long Noncoding ; Transcription Factors
Language	English
Publishing date	2022-01-12
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23020800
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Article: Profiling Cancer Cells by Cell-SELEX: Use of Aptamers for Discovery of Actionable Biomarkers and Therapeutic Applications Thereof.

Shigdar, Sarah / Agnello, Lisa / Fedele, Monica / Camorani, Simona / Cerchia, Laura

Pharmaceutics

2021 Volume 14, Issue 1

Abstract: The identification of tumor cell-specific surface markers is a key step towards personalized cancer medicine, allowing early assessment and accurate diagnosis, and development of efficacious targeted therapies. Despite significant efforts, currently the ... ...

Abstract	The identification of tumor cell-specific surface markers is a key step towards personalized cancer medicine, allowing early assessment and accurate diagnosis, and development of efficacious targeted therapies. Despite significant efforts, currently the spectrum of cell membrane targets associated with approved treatments is still limited, causing an inability to treat a large number of cancers. What mainly limits the number of ideal clinical biomarkers is the high complexity and heterogeneity of several human cancers and still-limited methods for molecular profiling of specific cancer types. Thanks to the simplicity, versatility and effectiveness of its application, cell-SELEX (Systematic Evolution of Ligands by Exponential Enrichment) technology is a valid complement to the present strategies for biomarkers' discovery. We and other researchers worldwide are attempting to apply cell-SELEX to the generation of oligonucleotide aptamers as tools for both identifying new cancer biomarkers and targeting them by innovative therapeutic strategies. In this review, we discuss the potential of cell-SELEX for increasing the currently limited repertoire of actionable cancer cell-surface biomarkers and focus on the use of the selected aptamers as components of innovative conjugates and nano-formulations for cancer therapy.
Language	English
Publishing date	2021-12-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics14010028
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Article ; Online: The Epithelial–Mesenchymal Transition at the Crossroads between Metabolism and Tumor Progression

Monica Fedele / Riccardo Sgarra / Sabrina Battista / Laura Cerchia / Guidalberto Manfioletti

International Journal of Molecular Sciences, Vol 23, Iss 800, p

2022 Volume 800

Abstract	The transition between epithelial and mesenchymal phenotype is emerging as a key determinant of tumor cell invasion and metastasis. It is a plastic process in which epithelial cells first acquire the ability to invade the extracellular matrix and migrate into the bloodstream via transdifferentiation into mesenchymal cells, a phenomenon known as epithelial–mesenchymal transition (EMT), and then reacquire the epithelial phenotype, the reverse process called mesenchymal–epithelial transition (MET), to colonize a new organ. During all metastatic stages, metabolic changes, which give cancer cells the ability to adapt to increased energy demand and to withstand a hostile new environment, are also important determinants of successful cancer progression. In this review, we describe the complex interaction between EMT and metabolism during tumor progression. First, we outline the main connections between the two processes, with particular emphasis on the role of cancer stem cells and LncRNAs. Then, we focus on some specific cancers, such as breast, lung, and thyroid cancer.
Keywords	epithelial–mesenchymal transition (EMT) ; metabolism ; cancer ; tumor progression ; Warburg effect ; metabolic rewiring ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	570
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Aptamers and antibodies

Lisa Agnello / Simona Camorani / Monica Fedele / Laura Cerchia

Exploration of Targeted Anti-tumor Therapy, Vol 2, Iss 1, Pp 107-

rivals or allies in cancer targeted therapy?

2021 Volume 121

Abstract	The goal of an efficacious cancer therapy is to specifically target diseased cells at high accuracy while sparing normal, healthy cells. Over the past three decades, immunotherapy, based on the use of monoclonal antibodies (mAbs) directed against tumor-associated antigens, to inhibit their oncogenic function, or against immune checkpoints, to modulate specific T cell responses against cancer, has proven to be an important strategy for cancer therapy. Nevertheless, the number of mAbs approved for clinical use is still limited because of significant drawbacks to their applicability. Oligonucleotide aptamers, similarly to antibodies, form high-affinity bonds with their specific protein targets, thus representing an effective tool for active cancer targeting. Compared to antibodies, aptamers’ use as therapeutic agents benefits from their low size, low/no immunogenicity, simple synthesis and design flexibility for improving efficacy and stability. This review intends to highlight recently emerged applications of aptamers as recognition elements, from biomarker discovery to targeted drug delivery and targeted treatment, showing aptamers’ potential to work in conjunction with antibodies for attacking cancer from multiple flanks.
Keywords	aptamers ; monoclonal antibodies ; targeted therapy ; theranostics ; selex ; Internal medicine ; RC31-1245
Subject code	616
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	Open Exploration Publishing Inc.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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