Related Experiment Video
Updated: Jul 31, 2025
Establishment and Characterization of Patient-Derived Xenograft Models of Anaplastic Thyroid Carcinoma and Head and Neck Squamous Cell Carcinoma
Published on: June 2, 2023
Proteasome inhibitors in medullary thyroid carcinoma: time to restart with clinical trials?
Giuseppe Fanciulli1,2, Roberta Modica3, Anna La Salvia4
1Neuroendocrine Tumor Unit, Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, Italy.
Introduction:
Medullary 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 Study:
This review aims to summarize the available in vitro and in vivo data about the role of PrIn in MTC.
Materials And Methods:
We 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.
Results:
Our 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.
Conclusion:
We 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.
Insights
Proteasome inhibitors show promise in preclinical studies for medullary thyroid cancer (MTC). However, clinical trials are scarce, suggesting a need for new trials to confirm their efficacy in improving patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Medullary thyroid cancer (MTC) is a rare malignancy with challenging advanced-stage management.
- Proteasome inhibitors (PrIn) are effective in various cancers by inhibiting cell proliferation and inducing apoptosis.
- PrIns offer potential therapeutic benefits for MTC patients, alone or in combination therapies.
Purpose of the Study:
- To review and summarize existing in vitro and in vivo data on the role of proteasome inhibitors in medullary thyroid cancer.
- To assess the current evidence for proteasome inhibitor efficacy in MTC treatment.
Main Methods:
- Conducted an extensive literature search of online databases (PubMed, Web of Science, Scopus) and clinical trial repositories.
- Utilized keywords including "medullary thyroid carcinoma" and specific proteasome inhibitor names (e.g., bortezomib, carfilzomib).
Main Results:
- Identified in vitro studies using proteasome inhibitors in MTC cell lines, both as monotherapy and in combination with other drugs.
- Found limited clinical trial data, with only two pertinent trials identified, some of which were prematurely interrupted.
Conclusions:
- A significant discrepancy exists between strong preclinical evidence and limited clinical trial data for proteasome inhibitors in MTC.
- Challenges in patient enrollment for rare diseases may hinder clinical trial progression.
- Further well-designed clinical trials are warranted to validate the therapeutic potential of proteasome inhibitors in MTC, potentially improving patient outcomes and survival.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:34Inhibition of Cdk Activity
01:15Drugs that Stabilize Microtubules