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Neuroendocrine neoplasms in the context of inherited tumor syndromes: a reappraisal focused on targeted therapies

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A Correction to this article was published on 07 October 2022

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Abstract

Purpose

Neuroendocrine neoplasms can occur as part of inherited disorders, usually in the form of well-differentiated, slow-growing tumors (NET). The main predisposing syndromes include: multiple endocrine neoplasias type 1 (MEN1), associated with a large spectrum of gastroenteropancreatic and thoracic NETs, and type 4 (MEN4), associated with a wide tumour spectrum similar to that of MEN1; von Hippel-Lindau syndrome (VHL), tuberous sclerosis (TSC), and neurofibromatosis 1 (NF-1), associated with pancreatic NETs. In the present review, we propose a reappraisal of the genetic basis and clinical features of gastroenteropancreatic and thoracic NETs in the setting of inherited syndromes with a special focus on molecularly targeted therapies for these lesions.

Methods

Literature search was systematically performed through online databases, including MEDLINE (via PubMed), and Scopus using multiple keywords’ combinations up to June 2022.

Results

Somatostatin analogues (SSAs) remain the mainstay of systemic treatment for NETs, and radiolabelled SSAs can be used for peptide-receptor radionuclide therapy for somatostatin receptor (SSTR)-positive NETs. Apart of these SSTR-targeted therapies, other targeted agents have been approved for NETs: the mTOR inhibitor everolimus for lung, gastroenteropatic and unknown origin NET, and sunitinib, an antiangiogenic tyrosine kinase inhibitor, for pancreatic NET. Novel targeted therapies with other antiangiogenic agents and immunotherapies have been also under evaluation.

Conclusions

Major advances in the understanding of genetic and epigenetic mechanisms of NET development in the context of inherited endocrine disorders have led to the recognition of molecular targetable alterations, providing a rationale for the implementation of treatments and development of novel targeted therapies.

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Acknowledgements

This review is part of the ‘Neuroendocrine Tumours Innovation Knowledge and Education’ project led by Prof. Annamaria Colao, Prof. Antongiulio Faggiano, and Professor Andrea Isidori, which aims at increasing the knowledge on neuroendocrine tumors. We would like to acknowledge all the Collaborators of this project: I. Aini, M. Albertelli, Y. Alessi, B. Altieri, S. Antonini, L. Barrea, F. Birtolo, F. Campolo, G. Cannavale, C. Cantone, S. Carra, R. Centello, A. Cozzolino, S. Di Molfetta, V. Di Vito, G. Fanciulli, T. Feola, F. Ferraù, S. Gay, E. Giannetta, F. Grillo, E. Grossrubatscher, V. Guarnotta, A. La Salvia, A. Laffi, A. Lania, A. Liccardi, P. Malandrino, R. Mazzilli, E. Messina, N Mikovic, R. Minotta, R. Modica, G. Muscogiuri, C. Pandozzi, G. Pugliese, G. Puliani, A. Ragni, M. Rubino, F. Russo, F. Sesti, L. Verde, A. Veresani, C. Vetrani, G. Vitale, V. Zamponi, and I. Zanata.

Funding

The research was not supported by any funding.

Author information

Authors and Affiliations

  1. Unit of Endocrinology, Department of Clinical and Experimental Medicine, University of Messina, AOU Policlinico “Gaetano Martino” University Hospital, 98125, Messina, Italy

    R. M. Ruggeri

  2. Department of Clinical Medicine and Surgery, Endocrinology Unit, University Federico II, Naples, Italy

    E. Benevento, E. Guadagno & A. Colao

  3. SSD Endocrine Disease and Diabetology, ASL TO3, Pinerolo, TO, Italy

    F. De Cicco

  4. Endocrinology Unit, Department of Clinical and Molecular Medicine, Sant’Andrea Hospital, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy

    B. Fazzalari & A. Faggiano

  5. Endocrinology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy

    I. Hasballa

  6. Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy

    M. G. Tarsitano

  7. Gruppo NETTARE, Policlinico Umberto I, Università Sapienza, Rome, Italy

    A. M. Isidori

  8. UNESCO Chair “Education for Health and Sustainable Development”, Federico II University, Naples, Italy

    A. Colao

Authors
  1. R. M. Ruggeri
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  2. E. Benevento
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  3. F. De Cicco
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  4. B. Fazzalari
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  5. E. Guadagno
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  6. I. Hasballa
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  7. M. G. Tarsitano
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  8. A. M. Isidori
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  9. A. Colao
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  10. A. Faggiano
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Consortia

on behalf of NIKE Group

  • I Aini
  • , M Albertelli
  • , Y Alessi
  • , B Altieri
  • , S Antonini
  • , L Barrea
  • , F Birtolo
  • , F Campolo
  • , G Cannavale
  • , C Cantone
  • , S Carra
  • , R Centello
  • , A Cozzolino
  • , S Molfetta
  • , V Vito
  • , G Fanciulli
  • , T Feola
  • , F Ferraù
  • , S Gay
  • , E Giannetta
  • , F Grillo
  • , E Grossrubatscher
  • , V Guarnotta
  • , A Salvia
  • , A Laffi
  • , A Lania
  • , A Liccardi
  • , P Malandrino
  • , R Mazzilli
  • , E Messina
  • , N Mikovic
  • , R Minotta
  • , R Modica
  • , G Muscogiuri
  • , C Pandozzi
  • , G Pugliese
  • , G Puliani
  • , A Ragni
  • , M Rubino
  • , F Russo
  • , F Sesti
  • , L Verde
  • , A Veresani
  • , C Vetrani
  • , G Vitale
  • , V Zamponi
  •  & I Zanata

Contributions

All authors made substantial contributions to the study conception and design. All authors approved the final version for submission for publication. All authors agree to be accountable for the accuracy and integrity of the work.

Corresponding author

Correspondence to R. M. Ruggeri.

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Conflict of interest

The authors have no financial or non-financial competing interests to disclose.

Ethical approval

The authors have no ethical conflict to disclose. The study was performed in accordance with the principles of the Declaration of Helsinki. Local Ethics Research Committee approval was obtained.

Informed consent

Written informed consent was obtained from the patients for publication of this case series.

Research involving human participants and/or animals

No animals were used for this study.

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Ruggeri, R.M., Benevento, E., De Cicco, F. et al. Neuroendocrine neoplasms in the context of inherited tumor syndromes: a reappraisal focused on targeted therapies. J Endocrinol Invest 46, 213–234 (2023). https://doi.org/10.1007/s40618-022-01905-4

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  • DOI: https://doi.org/10.1007/s40618-022-01905-4

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