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Article: Oral Adverse Events Associated with BRAF and MEK Inhibitors in Melanoma Treatment: A Narrative Literature Review.

Basilicata, Michele / Terrano, Vincenzo / D'Aurelio, Alessandro / Bruno, Giovanni / Troiani, Teresa / Bollero, Patrizio / Napolitano, Stefania

Healthcare (Basel, Switzerland)

2024 Volume 12, Issue 1

Abstract: Background: Melanoma cancer represents the most lethal type of skin cancer originating from the malignant transformation of melanocyte cells. Almost 50% of melanomas show the activation of BRAF mutations. The identification and characterization of BRAF ... ...

Abstract	Background: Melanoma cancer represents the most lethal type of skin cancer originating from the malignant transformation of melanocyte cells. Almost 50% of melanomas show the activation of BRAF mutations. The identification and characterization of BRAF mutations led to the development of specific drugs that radically changed the therapeutic approach to melanoma. Methods: We conducted a narrative review of the literature according to a written protocol before conducting the study. This article is based on previously conducted studies. We identified articles by searching electronic databases (Medline, Google Scholar and PubMed). We used a combination of "melanoma", "Braf-Mek inhibitors", " targeted therapy" and "oral side effects". Results: Eighteen studies were reported in this article showing the relationship between the use of targeted therapy in melanoma cancer and the development of oral side effects, such as mucositis, hyperkeratosis and cellular proliferation. Conclusion: Targeted therapy plays an important role in the treatment of melanoma cancer, showing a notable increase in response rate, prolonged progression-free survival and overall survival in BRAF-mutated melanoma patients. Oral side effects represent a common finding over the course of treatment. However, these adverse effects can be easily managed in a multidisciplinary approach involving collaboration between medical oncologists and dental doctors.
Language	English
Publishing date	2024-01-02
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2721009-1
ISSN	2227-9032
ISSN	2227-9032
DOI	10.3390/healthcare12010105
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Diagnostic value of liquid biopsy in the era of precision medicine: 10 years of clinical evidence in cancer.

Caputo, Vincenza / Ciardiello, Fortunato / Corte, Carminia Maria Della / Martini, Giulia / Troiani, Teresa / Napolitano, Stefania

Exploration of targeted anti-tumor therapy

2023 Volume 4, Issue 1, Page(s) 102–138

Abstract: Liquid biopsy is a diagnostic repeatable test, which in last years has emerged as a powerful tool for profiling cancer genomes in real-time with minimal invasiveness and tailoring oncological decision-making. It analyzes different blood-circulating ... ...

Abstract	Liquid biopsy is a diagnostic repeatable test, which in last years has emerged as a powerful tool for profiling cancer genomes in real-time with minimal invasiveness and tailoring oncological decision-making. It analyzes different blood-circulating biomarkers and circulating tumor DNA (ctDNA) is the preferred one. Nevertheless, tissue biopsy remains the gold standard for molecular evaluation of solid tumors whereas liquid biopsy is a complementary tool in many different clinical settings, such as treatment selection, monitoring treatment response, cancer clonal evolution, prognostic evaluation, as well as the detection of early disease and minimal residual disease (MRD). A wide number of technologies have been developed with the aim of increasing their sensitivity and specificity with acceptable costs. Moreover, several preclinical and clinical studies have been conducted to better understand liquid biopsy clinical utility. Anyway, several issues are still a limitation of its use such as false positive and negative results, results interpretation, and standardization of the panel tests. Although there has been rapid development of the research in these fields and recent advances in the clinical setting, many clinical trials and studies are still needed to make liquid biopsy an instrument of clinical routine. This review provides an overview of the current and future clinical applications and opening questions of liquid biopsy in different oncological settings, with particular attention to ctDNA liquid biopsy.
Language	English
Publishing date	2023-02-28
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2692-3114
ISSN (online)	2692-3114
DOI	10.37349/etat.2023.00125
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Article: The JAK-STAT Pathway as a Therapeutic Strategy in Cancer Patients with Immune Checkpoint Inhibitor-Induced Colitis: A Narrative Review.

Gravina, Antonietta Gerarda / Pellegrino, Raffaele / Esposito, Alfonso / Cipullo, Marina / Romeo, Mario / Palladino, Giovanna / Iodice, Patrizia / Federico, Alessandro / Troiani, Teresa

Cancers

2024 Volume 16, Issue 3

Abstract: Immunotherapy has emerged as a pivotal component in the treatment of various malignancies, encompassing lung, skin, gastrointestinal, and head and neck cancers. The foundation of this therapeutic approach lies in immune checkpoint inhibitors (ICI). While ...

Abstract	Immunotherapy has emerged as a pivotal component in the treatment of various malignancies, encompassing lung, skin, gastrointestinal, and head and neck cancers. The foundation of this therapeutic approach lies in immune checkpoint inhibitors (ICI). While ICIs have demonstrated remarkable efficacy in impeding the neoplastic progression of these tumours, their use may give rise to substantial toxicity, notably in the gastrointestinal domain, where ICI colitis constitutes a significant aspect. The optimal positioning of Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway inhibitors in the therapeutic management of ICI colitis remains unclear. Numerous reports have highlighted notable improvements in ICI colitis through the application of pan-JAK-STAT inhibitors, with tofacitinib, in particular, reporting evident clinical remission of colitis. The precise mechanism by which JAK-STAT inhibitors may impact the pathogenetic process of ICI colitis remains inadequately understood. However, there is speculation regarding their potential role in modulating memory resident CD8
Language	English
Publishing date	2024-01-31
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers16030611
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Article ; Online: Targeting the EGFR signalling pathway in metastatic colorectal cancer.

Napolitano, Stefania / Martini, Giulia / Ciardiello, Davide / Del Tufo, Sara / Martinelli, Erika / Troiani, Teresa / Ciardiello, Fortunato

The lancet. Gastroenterology & hepatology

2024

Abstract: Epidermal growth factor receptor (EGFR) and its activated downstream signalling pathways play a crucial role in colorectal cancer development and progression. After four decades of preclinical, translational, and clinical research, it has been shown that ...

Abstract	Epidermal growth factor receptor (EGFR) and its activated downstream signalling pathways play a crucial role in colorectal cancer development and progression. After four decades of preclinical, translational, and clinical research, it has been shown that blocking the EGFR signalling pathway at different molecular levels represents a fundamental therapeutic strategy for patients with metastatic colorectal cancer. Nevertheless, the efficacy of molecularly targeted therapies is inescapably limited by the insurgence of mechanisms of acquired cancer cell resistance. Thus, in the era of precision medicine, a deeper understanding of the complex molecular landscape of metastatic colorectal cancer is required to deliver the best treatment choices to all patients. Major efforts are currently ongoing to improve patient selection, improve the efficacy of available treatments targeting the EGFR pathway, and develop novel combination strategies to overcome therapy resistance within the continuum of care of metastatic colorectal cancer.
Language	English
Publishing date	2024-04-29
Publishing country	Netherlands
Document type	Journal Article ; Review
ISSN	2468-1253
ISSN (online)	2468-1253
DOI	10.1016/S2468-1253(23)00479-X
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Article ; Online: Towards the era of precision medicine in metastatic colorectal cancer.

Napolitano, Stefania / Troiani, Teresa / Martinelli, Erika / Ciardiello, Fortunato

ESMO open

2020 Volume 5, Issue 2

MeSH term(s)	Colorectal Neoplasms/epidemiology ; Humans ; Neoplasm Metastasis ; Precision Medicine/methods
Language	English
Publishing date	2020-03-27
Publishing country	England
Document type	Editorial
ISSN	2059-7029
ISSN (online)	2059-7029
DOI	10.1136/esmoopen-2020-000685
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Article: Current Landscape and Open Questions on Adjuvant Therapies in Melanoma.

De Falco, Vincenzo / Napolitano, Stefania / Guerrera, Luigi Pio / Troiani, Teresa

Dermatology practical & conceptual

2021 Volume 11, Issue Suppl 1, Page(s) e2021165S

Abstract: Melanoma is a form of skin cancer that is frequently diagnosed at early stages. In most cases, surgical resection is curative. In case of thicker melanomas (> pT1b) without clinical or instrumental evidence of metastasis, a sentinel lymph node biopsy is ... ...

Abstract	Melanoma is a form of skin cancer that is frequently diagnosed at early stages. In most cases, surgical resection is curative. In case of thicker melanomas (> pT1b) without clinical or instrumental evidence of metastasis, a sentinel lymph node biopsy is recommended for staging purposes. If the lymph nodes are the only site of disease (macroscopic or microscopic> 1mm), configuring stage III, the international guidelines recommend the use of adjuvant therapy with checkpoint inhibitors (nivolumab or pembrolizumab) or targeted therapies (dabrafenib plus trametinib). These drugs have shown a significant increase in recurrence-free survival, although some doubts and open questions remain. Specifically, none of the available treatments has shown a clear benefit in the overall survival rates, the advantages they give in stage IIIA are not well known, and finally there are still no prospective clinical studies identifying the best approach to continue the therapeutic process in case of relapse. Furthermore, there are new opportunities opening up with the upcoming results of the neoadjuvant trials that could revolutionize the treatment of clinically evident stage III melanoma.
Language	English
Publishing date	2021-07-01
Publishing country	Austria
Document type	Journal Article ; Review
ZDB-ID	2685397-8
ISSN	2160-9381
ISSN	2160-9381
DOI	10.5826/dpc.11S1a165S
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Article ; Online: A Novel EGFR Targeted Immunotoxin Based on Cetuximab and Type 1 RIP Quinoin Overcomes the Cetuximab Resistance in Colorectal Cancer Cells.

Landi, Nicola / Ciaramella, Vincenza / Ragucci, Sara / Chambery, Angela / Ciardiello, Fortunato / Pedone, Paolo V / Troiani, Teresa / Di Maro, Antimo

Toxins

2023 Volume 15, Issue 1

Abstract: Cetuximab is a monoclonal antibody blocking the epidermal growth factor receptor (EGFR) in metastatic colorectal cancer (mCRC). However, cetuximab treatment has no clinical benefits in patients affected by mCRC with KRAS mutation or in the presence of ... ...

Abstract	Cetuximab is a monoclonal antibody blocking the epidermal growth factor receptor (EGFR) in metastatic colorectal cancer (mCRC). However, cetuximab treatment has no clinical benefits in patients affected by mCRC with KRAS mutation or in the presence of constitutive activation of signalling pathways acting downstream of the EGFR. The aim of this study was to improve cetuximab's therapeutic action by conjugating cetuximab with the type 1 ribosome inactivating protein (RIP) quinoin isolated from quinoa seeds. A chemical conjugation strategy based on the use of heterobifunctional reagent succinimidyl 3-(2-pyridyldithio)propionate (SPDP) was applied to obtain the antibody-type 1 RIP chimeric immunoconjugate. The immunotoxin was then purified by chromatographic technique, and its enzymatic action was evaluated compared to quinoin alone. Functional assays were performed to test the cytotoxic action of the quinoin cetuximab immunoconjugate against the cetuximab-resistant GEO-CR cells. The novel quinoin cetuximab immunoconjugate showed a significant dose-dependent cytotoxicity towards GEO-CR cells, achieving IC
MeSH term(s)	Humans ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Cetuximab/pharmacology ; Cetuximab/genetics ; Cetuximab/therapeutic use ; Colonic Neoplasms/drug therapy ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/genetics ; ErbB Receptors/metabolism ; Immunotoxins/therapeutic use ; Mutation ; Saporins/therapeutic use ; Drug Resistance, Neoplasm
Chemical Substances	Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; Cetuximab (PQX0D8J21J) ; EGFR protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1) ; Immunotoxins ; Saporins (EC 3.2.2.22)
Language	English
Publishing date	2023-01-09
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2518395-3
ISSN	2072-6651 ; 2072-6651
ISSN (online)	2072-6651
ISSN	2072-6651
DOI	10.3390/toxins15010057
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Article: The Role of Sentinel Node Biopsy in the Era of Adjuvant Therapy for Melanoma.

Brancaccio, Gabriella / Briatico, Giulia / Scharf, Camila / Colella, Giuseppe / Docimo, Giovanni / Docimo, Ludovico / Faenza, Mario / Iovino, Francesco / Tolone, Salvatore / Verolino, Pasquale / Napolitano, Stefania / Troiani, Teresa / Ronchi, Andrea / Franco, Renato / Argenziano, Giuseppe

Dermatology practical & conceptual

2024 Volume 14, Issue 1

Abstract: Sentinel lymph node biopsy (SLNB) is a surgical procedure aimed to detect nodal metastases in patients with clinically occult disease. Since the advent of new systemic therapies, its role in melanoma has been extensively debated over the last years. In ... ...

Abstract	Sentinel lymph node biopsy (SLNB) is a surgical procedure aimed to detect nodal metastases in patients with clinically occult disease. Since the advent of new systemic therapies, its role in melanoma has been extensively debated over the last years. In this article, three possible scenarios are discussed, considering the SLNB impact on the management of melanoma patients. First, pT1b and pT2a patients with negative SLNB (stages IA and IB) and those with positive SLNB (stage IIIA) would all not benefit from adjuvant treatment. Therefore, SLNB might be avoided in these categories of patients. Second, in IIB and IIC, melanoma patients are already candidates for adjuvant treatment; therefore, SLNB in patients with T3b, T4a, or T4b melanoma would not change treatment decisions. On the other end of the spectrum, patients with pT2b and pT3a melanomas (clinical stage IIA) represent the only two groups whose management would be significantly affected by the SLNB status, being adjuvant therapy only indicated for SLN-positive patients. Further studies are needed to investigate which melanoma patient deserves SLNB.
Language	English
Publishing date	2024-01-01
Publishing country	Austria
Document type	Journal Article ; Review
ZDB-ID	2685397-8
ISSN	2160-9381
ISSN	2160-9381
DOI	10.5826/dpc.1401a38
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Article ; Online: All for one: Collaboration between dermatologist, radiation oncologist and radiologist in the clinical management of "difficult to treat" non melanoma skin cancer.

Gagliardi, Federico / Russo, Anna / Scharf, Camila / Pinto, Alessandro / Faenza, Mario / D'Ippolito, Emma / Argenziano, Giuseppe / Troiani, Teresa / Reginelli, Alfonso / Nardone, Valerio

Clinical and translational radiation oncology

2024 Volume 46, Page(s) 100774

Abstract: This series introduces the clinical management of difficult-to-treat non-melanoma skin cancers (NMSCs) through a multidisciplinary approach, emphasizing the integration of dermoscopy and Ultra high-frequency ultrasound (UHFUS) for accurate diagnosis and ... ...

Abstract	This series introduces the clinical management of difficult-to-treat non-melanoma skin cancers (NMSCs) through a multidisciplinary approach, emphasizing the integration of dermoscopy and Ultra high-frequency ultrasound (UHFUS) for accurate diagnosis and treatment planning, particularly in cases referred for radiotherapy (RT). Dermoscopy aids in diagnosing both pigmented and non-pigmented skin lesions, guiding treatment margins and reducing the benign-to-malignant biopsy ratio. UHFUS provides valuable insights into tumor size, depth, and vascularity, complementing clinical evaluations and assisting in RT planning. Three challenging cases are presented, highlighting the pivotal role of dermoscopy and UHFUS in decision-making and treatment optimization. Collaboration between dermatologists, radiation oncologists, and radiologists enhances diagnostic accuracy, tailoring treatment plans to individual patient needs and preferences, ultimately improving patient outcomes and experience. The integration of these imaging techniques holds promise for optimizing non-surgical treatments like RT and monitoring treatment progress, offering a personalized approach to NMSC management.
Language	English
Publishing date	2024-03-30
Publishing country	Ireland
Document type	Case Reports
ISSN	2405-6308
ISSN (online)	2405-6308
DOI	10.1016/j.ctro.2024.100774
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Article ; Online: Holistic Approach to Immune Checkpoint Inhibitor-Related Adverse Events.

Poto, Remo / Troiani, Teresa / Criscuolo, Gjada / Marone, Giancarlo / Ciardiello, Fortunato / Tocchetti, Carlo Gabriele / Varricchi, Gilda

Frontiers in immunology

2022 Volume 13, Page(s) 804597

Abstract: Immune checkpoint inhibitors (ICIs) block inhibitory molecules, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), or its ligand, programmed cell death protein ligand 1 (PD-L1) and enhance antitumor T- ... ...

Abstract	Immune checkpoint inhibitors (ICIs) block inhibitory molecules, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), or its ligand, programmed cell death protein ligand 1 (PD-L1) and enhance antitumor T-cell activity. ICIs provide clinical benefits in a percentage of patients with advanced cancers, but they are usually associated with a remarkable spectrum of immune-related adverse events (irAEs) (e.g., rash, colitis, hepatitis, pneumonitis, endocrine, cardiac and musculoskeletal dysfunctions). Particularly patients on combination therapy (e.g., anti-CTLA-4 plus anti-PD-1/PD-L1) experience some form of irAEs. Different mechanisms have been postulated to explain these adverse events. Host factors such as genotype, gut microbiome and pre-existing autoimmune disorders may affect the risk of adverse events. Fatal ICI-related irAEs are due to myocarditis, colitis or pneumonitis. irAEs usually occur within the first months after ICI initiation but can develop as early as after the first dose to years after ICI initiation. Most irAEs resolve pharmacologically, but some appear to be persistent. Glucocorticoids represent the mainstay of management of irAEs, but other immunosuppressive drugs can be used to mitigate refractory irAEs. In the absence of specific trials, several guidelines, based on data from retrospective studies and expert consensus, have been published to guide the management of ICI-related irAEs.
MeSH term(s)	B7-H1 Antigen ; Colitis ; Humans ; Immune Checkpoint Inhibitors/adverse effects ; Ligands ; Pneumonia ; Retrospective Studies
Chemical Substances	B7-H1 Antigen ; Immune Checkpoint Inhibitors ; Ligands
Language	English
Publishing date	2022-03-30
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.804597
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