Proteasome inhibitors in medullary thyroid carcinoma: time to restart with clinical trials?
IntroductionMedullary thyroid cancer (MTC) is a rare thyroid tumour whose management in advanced stages is challenging, despite effective therapeutic options having expanded in recent years. Proteasome inhibitors (PrIn) have shown the ability to improve patient outcomes, including survival and quali...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1145926/full |
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| author | Giuseppe Fanciulli Giuseppe Fanciulli Roberta Modica Anna La Salvia Erika Maria Grossrubatscher Tullio Florio Tullio Florio Francesco Ferraù Alessandro Veresani Flaminia Russo Annamaria Colao Annamaria Colao Antongiulio Faggiano |
| author_facet | Giuseppe Fanciulli Giuseppe Fanciulli Roberta Modica Anna La Salvia Erika Maria Grossrubatscher Tullio Florio Tullio Florio Francesco Ferraù Alessandro Veresani Flaminia Russo Annamaria Colao Annamaria Colao Antongiulio Faggiano |
| author_sort | Giuseppe Fanciulli |
| collection | DOAJ |
| description | IntroductionMedullary thyroid cancer (MTC) is a rare thyroid tumour whose management in advanced stages is challenging, despite effective therapeutic options having expanded in recent years. Proteasome inhibitors (PrIn) have shown the ability to improve patient outcomes, including survival and quality of life, in several malignancies, due to their ability to impair cell proliferation and cause apoptosis through the inhibition of the proteasome activity. Consequently, these drugs could represent a useful tool, alone or in combination with other treatments, in MTC patients.Aim of the studyThis review aims to summarize the available in vitro and in vivo data about the role of PrIn in MTC.Materials and methodsWe performed an extensive search for relevant data sources, including full-published articles in international online databases (PubMed, Web of Science, Scopus), preliminary reports in selected international meeting abstract repositories, and short articles published as supplements of international meetings, by using the following terms: medullary thyroid carcinoma, proteasome inhibitors, bortezomib, carfilzomib, ixazomib, delanzomib, marizomib, oprozomib, and MG132. Additionally, we conducted with the same keywords, an in-depth search in registered clinical trials repositories.ResultsOur search revealed in vitro studies in human and murine MTC cell lines, based on the use of PrIns, both alone and in combination with other anticancer drugs, and two pertinent clinical trials.ConclusionWe found a strong discrepancy between the evidence of PrIns effects in preclinical studies, and the scarcity or early interruption of clinical trials. We might speculate that difficulties in enrolling patients, as happens in other rare diseases, may have discouraged trials’ implementation in favor of drugs already approved for MTC. However, given the concrete improvement in the comprehension of the molecular basis of PrIn effects in MTC, new clinical trials with accurate inclusion criteria of enrollment might be warranted, in order to ascertain whether this treatment, alone or in combination with other drugs, could indeed represent an option to enhance the therapeutic response, and to ultimately improve patients’ outcome and survival. |
| first_indexed | 2024-04-09T17:11:14Z |
| format | Article |
| id | doaj.art-36202e21218e4218aff337283e269182 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-09T17:11:14Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-36202e21218e4218aff337283e2691822023-04-20T05:58:53ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-04-011410.3389/fendo.2023.11459261145926Proteasome inhibitors in medullary thyroid carcinoma: time to restart with clinical trials?Giuseppe Fanciulli0Giuseppe Fanciulli1Roberta Modica2Anna La Salvia3Erika Maria Grossrubatscher4Tullio Florio5Tullio Florio6Francesco Ferraù7Alessandro Veresani8Flaminia Russo9Annamaria Colao10Annamaria Colao11Antongiulio Faggiano12Neuroendocrine Tumor Unit, Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, ItalyEndocrine Unit, Azienda Ospedaliero-Universitaria (AOU) Sassari, Sassari, ItalyEndocrinology, Diabetology and Andrology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, ItalyNational Center for Drug Research and Evaluation, National Institute of Health (ISS), Rome, ItalyEndocrine Unit, Azienda Socio Sanitaria Territoriale (ASST) Grande Ospedale Metropolitano Niguarda, Milan, ItalyDepartment of Internal Medicine, University of Genoa, Genoa, ItalyScientific Institute for Research, Hospitalisation and Healthcare Ospedale Policlinico San Martino, Genoa, ItalyDepartment of Human Pathology of Adulthood and Childhood “G. Barresi” (DETEV), University of Messina, Messina, ItalyEndocrinology Unit, Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, Genoa, Italy0Endocrinology Unit, Department of Clinical and Molecular Medicine, The European Neuroendocrine Tumor Society (ENETS) Center of Excellence, Sant’Andrea Hospital, Sapienza University of Rome, Rome, ItalyEndocrinology, Diabetology and Andrology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy1UNESCO Chair, Education for Health and Sustainable Development, Federico II University, Naples, Italy0Endocrinology Unit, Department of Clinical and Molecular Medicine, The European Neuroendocrine Tumor Society (ENETS) Center of Excellence, Sant’Andrea Hospital, Sapienza University of Rome, Rome, ItalyIntroductionMedullary thyroid cancer (MTC) is a rare thyroid tumour whose management in advanced stages is challenging, despite effective therapeutic options having expanded in recent years. Proteasome inhibitors (PrIn) have shown the ability to improve patient outcomes, including survival and quality of life, in several malignancies, due to their ability to impair cell proliferation and cause apoptosis through the inhibition of the proteasome activity. Consequently, these drugs could represent a useful tool, alone or in combination with other treatments, in MTC patients.Aim of the studyThis review aims to summarize the available in vitro and in vivo data about the role of PrIn in MTC.Materials and methodsWe performed an extensive search for relevant data sources, including full-published articles in international online databases (PubMed, Web of Science, Scopus), preliminary reports in selected international meeting abstract repositories, and short articles published as supplements of international meetings, by using the following terms: medullary thyroid carcinoma, proteasome inhibitors, bortezomib, carfilzomib, ixazomib, delanzomib, marizomib, oprozomib, and MG132. Additionally, we conducted with the same keywords, an in-depth search in registered clinical trials repositories.ResultsOur search revealed in vitro studies in human and murine MTC cell lines, based on the use of PrIns, both alone and in combination with other anticancer drugs, and two pertinent clinical trials.ConclusionWe found a strong discrepancy between the evidence of PrIns effects in preclinical studies, and the scarcity or early interruption of clinical trials. We might speculate that difficulties in enrolling patients, as happens in other rare diseases, may have discouraged trials’ implementation in favor of drugs already approved for MTC. However, given the concrete improvement in the comprehension of the molecular basis of PrIn effects in MTC, new clinical trials with accurate inclusion criteria of enrollment might be warranted, in order to ascertain whether this treatment, alone or in combination with other drugs, could indeed represent an option to enhance the therapeutic response, and to ultimately improve patients’ outcome and survival.https://www.frontiersin.org/articles/10.3389/fendo.2023.1145926/fullmedullary thyroid carcinomaproteasome inhibitorsbortezomibcarfilzomibixazomibMG132 |
| spellingShingle | Giuseppe Fanciulli Giuseppe Fanciulli Roberta Modica Anna La Salvia Erika Maria Grossrubatscher Tullio Florio Tullio Florio Francesco Ferraù Alessandro Veresani Flaminia Russo Annamaria Colao Annamaria Colao Antongiulio Faggiano Proteasome inhibitors in medullary thyroid carcinoma: time to restart with clinical trials? Frontiers in Endocrinology medullary thyroid carcinoma proteasome inhibitors bortezomib carfilzomib ixazomib MG132 |
| title | Proteasome inhibitors in medullary thyroid carcinoma: time to restart with clinical trials? |
| title_full | Proteasome inhibitors in medullary thyroid carcinoma: time to restart with clinical trials? |
| title_fullStr | Proteasome inhibitors in medullary thyroid carcinoma: time to restart with clinical trials? |
| title_full_unstemmed | Proteasome inhibitors in medullary thyroid carcinoma: time to restart with clinical trials? |
| title_short | Proteasome inhibitors in medullary thyroid carcinoma: time to restart with clinical trials? |
| title_sort | proteasome inhibitors in medullary thyroid carcinoma time to restart with clinical trials |
| topic | medullary thyroid carcinoma proteasome inhibitors bortezomib carfilzomib ixazomib MG132 |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1145926/full |
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