Adverse events associated with mTOR inhibitors

Pallet, Nicolas; Legendre, Christophe

doi:10.1517/14740338.2013.752814

Cited by 198PI3K/AKT/mTOR signaling in cancerAdvanced Breast Cancer TherapiesPharmacovigilance and Adverse Drug Reactions

Adverse events associated with mTOR inhibitors

Pallet, Nicolas, Legendre, Christophe·2013·Expert Opinion on Drug Safety

DOI 10.1517/14740338.2013.752814

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Abstract

INTRODUCTION: The mTOR (mechanistic target of rapamycin, formerly known as mammalian target of rapamycin) kinase is centrally involved in the regulation of cell growth and metabolism in response to intra- and extracellular energetic stimuli and growth factors. The importance of mTOR in health and diseases has fueled the development of molecules that inhibit mTOR signaling, including rapalogs (sirolimus, temsirolimus, everolimus and deforolimus), which complex with FK506-binding protein 12 (FK-BP12) to inhibit mTOR complex 1 (MTORC1) activity in an allosteric manner, or the more recent ATP-competitive mTOR inhibitors (mTORi), which target the catalytic site of the enzyme. However, clinical development of these mTORi has revealed that these drugs produced numerous side effects that could be serious and/or debilitating. Despite pharmacological efforts to develop drugs with an improved safety profile, these side effects are often unpredictable and may frequently preclude the efficiency of mTORi. AREAS COVERED: The objective of this review is to perform a comprehensive survey of the safety profiles of various rapalog-based therapies from the available clinical literature. The authors will discuss the potential mechanisms of these therapies, taking into account the knowledge of the biological pathways regulated by mTOR. EXPERT OPINION: A better prevention and management of mTORi-related side effects requires the identification of alterations in related biological pathways that will help to delineate therapeutic targets.

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Drawbacks of chronic rapamycin therapy include cytopenias, nephrotoxicity, metabolic syndrome, dermatitis, and pneumonitis.
“the drawbacks of chronic rapamcyin therapy – including cytopenias, nephrotoxicity, metabolic syndrome, dermatitis, and pneumonitis [502,503] – are well known.”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [503]

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Authors: Pallet, N., & Legendre, C.
Affiliations: Inserm (FR)
Hôpital Necker-Enfants Malades (FR)
ORCID: Pallet, Nicolas
Legendre, Christophe
Venue: Expert Opinion on Drug Safety
Publisher: Informa UK Limited
Published: 2012-12-20
Volume: 12
Issue: 2
Pages: 177-186
ISSN: 1474-0338 (ISSN-L)
1744-764X
DOI: 10.1517/14740338.2013.752814
OpenAlex: W2092342666
Cited by: 198
References: 94
Citations by year: 2026: 9 · 2025: 10 · 2024: 9 · 2023: 20 · 2022: 18 · 2021: 13 · 2020: 15 · 2019: 20 · 2018: 17 · 2017: 17 · 2016: 21 · 2015: 17 · 2014: 6 · 2013: 6
FWCI: 0.85
Type: journal article
Language: en
Open access: closed
Locations: Expert Opinion on Drug Safety (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Advanced Breast Cancer Therapies
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
Keywords: mTOR inhibitors, adverse drug reactions, rapalogs, rapamycin, temsirolimus, everolimus, FKBP12, mTORC1, drug safety
MeSH terms: Everolimus, Animals, Antineoplastic Agents, Clinical Trials as Topic, Humans, Immunosuppressive Agents, Sirolimus, Protein Kinase Inhibitors, Dyslipidemias, TOR Serine-Threonine Kinases

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