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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

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: The Management of Phaeochromocytomas and Paragangliomas in the Era of Precision Medicine: Where Are We Now? Evidence-Based Systemic Treatment Options and Future Cluster Oriented Perspectives.

Bracigliano, Alessandra / Marretta, Antonella Lucia / Guerrera, Luigi Pio / Simioli, Roberto / Clemente, Ottavia / Granata, Vincenza / Minopoli, Anita / Della Vittoria Scarpati, Giuseppina / Picozzi, Fernanda / Cannella, Lucia / Pizzolorusso, Antonio / Di Gennaro, Francesca / Tafuto, Roberto / Sarno, Maria Rosaria / Cavalcanti, Ernesta / Ribera, Dario / Tafuto, Salvatore

Pharmaceuticals (Basel, Switzerland)

2024 Volume 17, Issue 3

Abstract: Pheochromocytomas (PCCs) and Paragangliomas (PGLs), commonly known as PPGLs to include both entities, are rare neuroendocrine tumors that may arise in the context of hereditary syndromes or be sporadic. However, even among sporadic PPGLs, identifiable ... ...

Abstract	Pheochromocytomas (PCCs) and Paragangliomas (PGLs), commonly known as PPGLs to include both entities, are rare neuroendocrine tumors that may arise in the context of hereditary syndromes or be sporadic. However, even among sporadic PPGLs, identifiable somatic alterations in at least one of the known susceptibility genes can be detected. Therefore, about 3/4 of all PPGL patients can be assigned to one of the three molecular clusters that have been identified in the last years with difference in the underlying pathogenetic mechanisms, biochemical phenotype, metastatic potential, and prognosis. While surgery represents the mainstay of treatment for localized PPGLs, several therapeutic options are available in advanced and/or metastatic setting. However, only few of them hinge upon prospective data and a cluster-oriented approach has not yet been established. In order to render management even more personalized and improve the prognosis of this molecularly complex disease, it is undoubtable that genetic testing for germline mutations as well as genome profiling for somatic mutations, where available, must be improved and become standard practice. This review summarizes the current evidence regarding diagnosis and treatment of PPGLs, supporting the need of a more cluster-specific approach in clinical practice.
Language	English
Publishing date	2024-03-08
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph17030354
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Article: Extrapulmonary Neuroendocrine Carcinomas: Current Management and Future Perspectives.

Stumpo, Sara / Formelli, Maria Giovanna / Persano, Irene / Parlagreco, Elena / Lauricella, Eleonora / Rodriquenz, Maria Grazia / Guerrera, Luigi Pio / Zurlo, Ina Valeria / Campana, Davide / Brizzi, Maria Pia / Cives, Mauro / La Salvia, Anna / Lamberti, Giuseppe

Journal of clinical medicine

2023 Volume 12, Issue 24

Abstract: Neuroendocrine carcinomas (NECs) are poorly differentiated and highly aggressive epithelial neuroendocrine neoplasms. The most common primary site is the lung, but they may arise in every organ. Approximately 37% of extrapulmonary NECs (EP-NECs) occur in ...

Abstract	Neuroendocrine carcinomas (NECs) are poorly differentiated and highly aggressive epithelial neuroendocrine neoplasms. The most common primary site is the lung, but they may arise in every organ. Approximately 37% of extrapulmonary NECs (EP-NECs) occur in the gastroenteropancreatic (GEP) tract, followed by the genitourinary (GU) system and gynecological tract. As a result of their rarity, there is scant evidence to guide treatment recommendations, and a multidisciplinary approach is essential for the management of such patients. Platinum-based chemotherapy currently represents the standard of care for EP-NECs of any site, mirroring the management of small-cell lung cancer (SCLC), but further approaches are still under investigation. Indeed, ongoing trials evaluating targeted therapies, immune checkpoint inhibitors (ICIs), and radionuclide therapy could provide potentially breakthrough therapeutic options. Given the relative dearth of evidence-based literature on these orphan diseases, the aim of this review is to provide an overview of the pathology and current treatment options, as well as to shed light on the most pressing unmet needs in the field.
Language	English
Publishing date	2023-12-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm12247715
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Article ; Online: Comprehensive Review on the Clinical Relevance of Long Non-Coding RNAs in Cutaneous Melanoma.

De Falco, Vincenzo / Napolitano, Stefania / Esposito, Daniela / Guerrera, Luigi Pio / Ciardiello, Davide / Formisano, Luigi / Troiani, Teresa

International journal of molecular sciences

2021 Volume 22, Issue 3

Abstract: Cutaneous melanoma is considered a rare tumor, although it is one of the most common cancers in young adults and its incidence has risen in the last decades. Targeted therapy, with BRAF and MEK inhibitors, and immunotherapy revolutionized the treatment ... ...

Abstract	Cutaneous melanoma is considered a rare tumor, although it is one of the most common cancers in young adults and its incidence has risen in the last decades. Targeted therapy, with BRAF and MEK inhibitors, and immunotherapy revolutionized the treatment of metastatic melanoma but there is still a considerable percentage of patients with primary or acquired resistance to these therapies. Recently, oncology researchers directed their attention at the role of long non-coding RNAs (lncRNAs) in different types of cancers, including melanoma. lncRNAs are RNA transcripts, initially considered "junk sequences", that have been proven to have a crucial role in the fine regulation of physiological and pathological processes of different tissues. Furthermore, they are more expressed in tumors than protein-coding genes, constituting perfect candidates either as biomarkers (diagnostic, prognostic, predictive) or as therapeutic targets. In this work, we reviewed all the literature available for lncRNA in melanoma, elucidating all the potential roles in this tumor.
MeSH term(s)	Animals ; Biomarkers, Tumor ; Body Fluids ; Cell-Free Nucleic Acids ; Gene Expression Regulation, Neoplastic ; Humans ; Melanoma/diagnosis ; Melanoma/genetics ; Melanoma/therapy ; Mutation ; Neoplasm Staging ; Prognosis ; Proto-Oncogene Proteins B-raf/genetics ; RNA, Long Noncoding/genetics ; Skin Neoplasms/diagnosis ; Skin Neoplasms/genetics ; Skin Neoplasms/therapy ; Melanoma, Cutaneous Malignant
Chemical Substances	Biomarkers, Tumor ; Cell-Free Nucleic Acids ; RNA, Long Noncoding ; BRAF protein, human (EC 2.7.11.1) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1)
Language	English
Publishing date	2021-01-25
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/ijms22031166
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Article ; Online: Cancer Treatment-Induced Bone Loss (CTIBL): State of the Art and Proper Management in Breast Cancer Patients on Endocrine Therapy.

Diana, Anna / Carlino, Francesca / Giunta, Emilio Francesco / Franzese, Elisena / Guerrera, Luigi Pio / Di Lauro, Vincenzo / Ciardiello, Fortunato / Daniele, Bruno / Orditura, Michele

Current treatment options in oncology

2021 Volume 22, Issue 5, Page(s) 45

Abstract: Opinion statement: About 70-80% of early breast cancer (BC) patients receive adjuvant endocrine therapy (ET) for at least 5 years. ET includes in the majority of cases the use of aromatase inhibitors, as upfront or switch strategy, that lead to impaired ...

Abstract	Opinion statement: About 70-80% of early breast cancer (BC) patients receive adjuvant endocrine therapy (ET) for at least 5 years. ET includes in the majority of cases the use of aromatase inhibitors, as upfront or switch strategy, that lead to impaired bone health. Given the high incidence and also the high prevalence of BC, cancer treatment-induced bone loss (CTIBL) represents the most common long-term adverse event experimented by patients with hormone receptor positive tumours. CTIBL is responsible for osteoporosis occurrence and, as a consequence, fragility fractures that may negatively affect quality of life and survival expectancy. As recommended by main international guidelines, BC women on aromatase inhibitors should be carefully assessed for their fracture risk at baseline and periodically reassessed during adjuvant ET in order to early detect significant worsening in terms of bone health. Antiresorptive agents, together with adequate intake of calcium and vitamin D, should be administered in BC patients during all course of ET, especially in those at high risk of osteoporotic fractures, as calculated by tools available for clinicians. Bisphosphonates, such as zoledronate or pamidronate, and anti-RANKL antibody, denosumab, are the two classes of antiresorptive drugs used in clinical practice with similar efficacy in preventing bone loss induced by aromatase inhibitor therapy. The choice between them, in the absence of direct comparison, should be based on patients' preference and compliance; the different safety profile is mainly related to the route of administration, although both types of drugs are manageable with due care, since most of the adverse events are predictable and preventable. Despite advances in management of CTIBL, several issues such as the optimal time of starting antiresorptive agents and the duration of treatment remain unanswered. Future clinical trials as well as increased awareness of bone health are needed to improve prevention, assessment and treatment of CTIBL in these long-term survivor patients.
MeSH term(s)	Antineoplastic Agents/adverse effects ; Aromatase Inhibitors/adverse effects ; Bone Density/drug effects ; Bone Density Conservation Agents/therapeutic use ; Breast Neoplasms/drug therapy ; Denosumab/therapeutic use ; Diphosphonates/therapeutic use ; Female ; Fractures, Bone/prevention & control ; Humans ; Osteoporosis/chemically induced ; Osteoporosis/diagnosis ; Osteoporosis/therapy
Chemical Substances	Antineoplastic Agents ; Aromatase Inhibitors ; Bone Density Conservation Agents ; Diphosphonates ; Denosumab (4EQZ6YO2HI)
Language	English
Publishing date	2021-04-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2057351-0
ISSN	1534-6277 ; 1527-2729
ISSN (online)	1534-6277
ISSN	1527-2729
DOI	10.1007/s11864-021-00835-2
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Article: Mixed Neuroendocrine Non-Neuroendocrine Neoplasms of the Gastrointestinal Tract: A Case Series.

Guerrera, Luigi Pio / Suarato, Gabriella / Napolitano, Rossella / Perrone, Alessandra / Caputo, Vincenza / Ventriglia, Anna / Martini, Giulia / Della Corte, Carminia Maria / Orditura, Michele / Martinelli, Erika / Ciardiello, Fortunato / Montella, Marco / Franco, Renato / Troiani, Teresa / Napolitano, Stefania

Healthcare (Basel, Switzerland)

2022 Volume 10, Issue 4

Abstract: Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) refer to heterogenous rare neoplasms constituted of at least a neuroendocrine population-either well-differentiated, or more frequently poorly differentiated-and a non-neuroendocrine population, ... ...

Abstract	Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) refer to heterogenous rare neoplasms constituted of at least a neuroendocrine population-either well-differentiated, or more frequently poorly differentiated-and a non-neuroendocrine population, both accounting for at least 30% of the whole tumor mass. Several studies recently focused on the key genetic and epigenetic changes underlying MiNENs to better understand how they develop, and explore biological similarities among the two components and their pure counterparts. However, their molecular landscape still remains poorly understood. NGS may represent a useful tool to study this orphan disease by detecting the main genetic alterations and possible therapeutic targets. NGS analysis on tissue and/or blood samples through the Foundation One (F1) platform was performed on consecutive samples collected from four patients diagnosed with MiNENs of the gastroenteric tract. Several genetic alterations were shared among samples from the same patients, thus suggesting a common origin between them, although morphology sometimes changed at histopathological evaluation. Common molecular alterations among samples from different patients that had not been previously described to our knowledge were also detected. Finally, it is of the utmost importance to clarify if the maintenance of the 30% cut-off is still essential in defining MiNENs and really manages to include all of the mixed neoplasms.
Language	English
Publishing date	2022-04-11
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2721009-1
ISSN	2227-9032
ISSN	2227-9032
DOI	10.3390/healthcare10040708
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Article ; Online: Immunotherapy in advanced anal cancer: Is the beginning of a new era?

Ciardiello, Davide / Guerrera, Luigi Pio / Maiorano, Brigida Anna / Parente, Paola / Latiano, Tiziana Pia / Di Maio, Massimo / Ciardiello, Fortunato / Troiani, Teresa / Martinelli, Erika / Maiello, Evaristo

Cancer treatment reviews

2022 Volume 105, Page(s) 102373

Abstract: For decades metastatic squamous cell carcinoma of the anus (SCCA)has been considered a rare disease with very limited treatment options and a dismal prognosis. Prior to 2017, no data from prospective studies on the management of metastatic SCCA were ... ...

Abstract	For decades metastatic squamous cell carcinoma of the anus (SCCA)has been considered a rare disease with very limited treatment options and a dismal prognosis. Prior to 2017, no data from prospective studies on the management of metastatic SCCA were available with scant information from retrospective analyses and few treatment options. Recently, InterAAct trial showed an advantage of carboplatin plus paclitaxel over the historical standard of care represented by cisplatin plus 5-fluorouracil. Unfortunately, there is no established second-line treatment after progression to first-line platinum-based chemotherapy. Interestingly, a better understanding of the immunobiology of the neoplasm and the strict association between HPV/HIV infection and tumor microenvironment led to the development of immunotherapies. Emerging evidence suggests that the use of anti-PD1/PD-L1 agents could lead to promising antitumor activity in a subgroup of patients with pre-treated anal cancer, opening new therapeutic scenarios. Here, we will focus on completed clinical trials evaluating immunotherapy in patients with (SCCA), pointing out the future perspectives and possible biomarkers of response.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Anus Neoplasms/therapy ; HIV Infections/drug therapy ; Humans ; Immunotherapy ; Prospective Studies ; Retrospective Studies ; Tumor Microenvironment
Language	English
Publishing date	2022-03-08
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	125102-8
ISSN	1532-1967 ; 0305-7372
ISSN (online)	1532-1967
ISSN	0305-7372
DOI	10.1016/j.ctrv.2022.102373
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Article ; Online: Immunotherapy for Biliary Tract Cancer in the Era of Precision Medicine: Current Knowledge and Future Perspectives.

Ciardiello, Davide / Maiorano, Brigida Anna / Parente, Paola / Rodriquenz, Maria Grazia / Latiano, Tiziana Pia / Chiarazzo, Cinzia / Pazienza, Valerio / Guerrera, Luigi Pio / Amoruso, Brunella / Normanno, Nicola / Martini, Giulia / Ciardiello, Fortunato / Martinelli, Erika / Maiello, Evaristo

International journal of molecular sciences

2022 Volume 23, Issue 2

Abstract: Biliary tract cancers (BTC) represent a heterogeneous and aggressive group of tumors with dismal prognosis. For a long time, BTC has been considered an orphan disease with very limited therapeutic options. In recent years a better understanding of the ... ...

Abstract	Biliary tract cancers (BTC) represent a heterogeneous and aggressive group of tumors with dismal prognosis. For a long time, BTC has been considered an orphan disease with very limited therapeutic options. In recent years a better understanding of the complex molecular landscape of biology is rapidly changing the therapeutic armamentarium. However, while 40-50% of patients there are molecular drivers susceptible to target therapy, for the remaining population new therapeutic options represent an unsatisfied clinical need. The role of immunotherapy in the continuum of treatment of patients with BTC is still debated. Despite initial signs of antitumor-activity, single-agent immune checkpoint inhibitors (ICIs) demonstrated limited efficacy in an unselected population. Therefore, identifying the best partner to combine ICIs and predictive biomarkers represents a key challenge to optimize the efficacy of immunotherapy. This review provides a critical analysis of completed trials, with an eye on future perspectives and possible biomarkers of response.
MeSH term(s)	Animals ; Antineoplastic Agents, Immunological/pharmacology ; Antineoplastic Agents, Immunological/therapeutic use ; Biliary Tract Neoplasms/diagnosis ; Biliary Tract Neoplasms/etiology ; Biliary Tract Neoplasms/metabolism ; Biliary Tract Neoplasms/therapy ; Biomarkers, Tumor ; Clinical Trials as Topic ; Combined Modality Therapy/methods ; Disease Management ; Disease Susceptibility ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Molecular Targeted Therapy/methods ; Precision Medicine/methods ; Prognosis ; Treatment Outcome
Chemical Substances	Antineoplastic Agents, Immunological ; Biomarkers, Tumor
Language	English
Publishing date	2022-01-13
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/ijms23020820
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Article ; Online: Q-switched 1064 nm Nd-Yag nanosecond laser effects on skin barrier function and on molecular rejuvenation markers in keratinocyte-fibroblasts interaction.

De Filippis, Anna / Perfetto, Brunella / Guerrera, Luigi Pio / Oliviero, Giovanni / Baroni, Adone

Lasers in medical science

2018 Volume 34, Issue 3, Page(s) 595–605

Abstract: Skin represents an interface between internal and external environment; it protects human body by regulating the water loss and the maintenance of body temperature, defending against irritant and pathogen agents, and against physical, chemical, and UV ... ...

Abstract	Skin represents an interface between internal and external environment; it protects human body by regulating the water loss and the maintenance of body temperature, defending against irritant and pathogen agents, and against physical, chemical, and UV damage. It provides to essential physiological functions, such as the important antioxidant defense capacity; its protective/defensive function is performed by a high number of proteins, and shows important functions in maintenance of skin barrier homeostasis. Keratinocytes and fibroblasts play a pivotal role to determine or prevent skin aging in response to intrinsic or extrinsic stimuli, modulating cytokines and several biochemical factors. Non-ablative technologies are playing an increasing role in the management of skin aging, inducing a dermal remodeling without a visible epidermal damage. The objective of this study was to evaluate the effect of Q-switched 1064 Nd-YAG laser (Medlite Conbio C6 Nd-YAG laser, Cynosure USA) in skin barrier function, analyzing the constituents which are strongly altered in aging skin. Particularly, we evaluated the expression of filaggrin, TGase, HSP70, and aquaporins, on HaCaT cells. The expression of proinflammatory cytokines has been investigated too.As a second step of the study, we analyzed the modulation of the rejuvenation molecular markers on human skin fibroblasts (HDFs) stimulated with keratinocytes conditioned medium (KCM).Our results demonstrated that Q-switched 1064 nm Nd:YAG laser acts on the skin barrier function, increasing the expression of aquaporins, filaggrin, TGase, and HSP70, modulating the proinflammatory cytokines. In fibroblasts stimulated with keratinocytes conditioned medium (KCM) and irradiated with Q-switched 1064 nm Nd:YAG laser, we can observe a reduction of MMP-1 and an increase in procollagen, collagen type I, and elastin. Our results highlight that Q-switched 1064 nm Nd:YAG laser treatment could represent an effective weapon to fight skin aging.
MeSH term(s)	Biomarkers/metabolism ; Cell Communication/radiation effects ; Cell Line ; Cell Survival/radiation effects ; Cytokines/genetics ; Cytokines/metabolism ; Fibroblasts/cytology ; Fibroblasts/radiation effects ; Gene Expression Regulation/radiation effects ; Humans ; Inflammation Mediators/metabolism ; Keratinocytes/cytology ; Keratinocytes/radiation effects ; Lasers, Solid-State/therapeutic use ; Rejuvenation ; Skin/radiation effects ; Skin Aging/radiation effects ; Water
Chemical Substances	Biomarkers ; Cytokines ; Inflammation Mediators ; Water (059QF0KO0R)
Language	English
Publishing date	2018-10-01
Publishing country	England
Document type	Journal Article
ZDB-ID	632808-8
ISSN	1435-604X ; 0268-8921
ISSN (online)	1435-604X
ISSN	0268-8921
DOI	10.1007/s10103-018-2635-1
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Article: Clinical Utility of Liquid Biopsy to Detect BRAF and NRAS Mutations in Stage III/IV Melanoma Patients by Using Real-Time PCR.

Giunta, Emilio Francesco / De Falco, Vincenzo / Vitiello, Pietro Paolo / Guerrera, Luigi Pio / Suarato, Gabriella / Napolitano, Rossella / Perrone, Alessandra / Argenziano, Giuseppe / Franco, Renato / Caraglia, Michele / Martinelli, Erika / Ciardiello, Davide / Ciardiello, Fortunato / Napolitano, Stefania / Troiani, Teresa

Cancers

2022 Volume 14, Issue 13

Abstract: Background: Liquid biopsy is a potentially useful tool for melanoma patients, also for detecting BRAS/NRAS mutations, even if the tissue analysis remains the current standard.: Methods: In this work, we tested ctDNA on plasma samples from 56 BRAF- ... ...

Abstract	Background: Liquid biopsy is a potentially useful tool for melanoma patients, also for detecting BRAS/NRAS mutations, even if the tissue analysis remains the current standard. Methods: In this work, we tested ctDNA on plasma samples from 56 BRAF-V600/NRAS mutant stage III/IV melanoma patients using a real-time quantitative PCR (qPCR)-based platform. The study population was divided into two cohorts: the first including 26 patients who had undergone radical resection (resected cohort) and the second including 30 patients who had unresected measurable disease (advanced cohort). Moreover, for 10 patients in the advanced cohort, ctDNA assessment was repeated at specified timepoints after baseline testing. Data were analyzed and correlated to the clinicopathologic characteristics and outcomes. Results: In the baseline cohort, a higher tissue-plasma concordance was seen in patients with high burden of disease (sum of diameters ≥30 mm, ≥2 metastatic sites, elevated LDH levels); furthermore, monitoring of these patients through ctDNA analysis was informative for therapeutic responses. On the other hand, the low sensitivity of this technique did not allow for clinically valuable prediction of relapses in radically resected stage III/IV patients. Conclusions: Overall, our data suggest that qPCR-based ctDNA analysis could be informative in a subset of locally advanced and metastatic melanoma patients with specific clinical-radiological characteristics, supporting further investigations in this setting.
Language	English
Publishing date	2022-06-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14133053
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