Everolimus is a new anti-cancer molecule: Metabolic side effects as lipid disorders and hyperglycemia

Morviducci, Lelio; Rota, Francesca Silvia; Rizzà, Laura; Giacinto, Paola Di; Ramponi, Simona; Nardone, Maria Rosaria; Tubili, Claudio; Lenzi, Andrea; Zuppi, Paolo; Baldelli, Roberto

doi:10.1016/j.diabres.2018.04.001

Cited by 32 publications

(38 citation statements)

References 8 publications

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“…These trials have revealed that this class of drugs was also quite well tolerated in childhood patients in general, except for one study. Nevertheless, well-known adverse effects of everolimus and temsirolimus include hyperglycemia, dyslipidemia, mouth ulceration, stomatitis, increased susceptibility to infections, interstitial pneumonitis, vomiting, and diarrhea [ 97 , 167 , 168 , 169 ].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Targeting of mTOR in T-Cell Acute Lymphoblastic Leukemia: An Update

Evangelisti

Chiarini

McCubrey

et al. 2018

IJMS

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T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive blood malignancy that arises from the clonal expansion of transformed T-cell precursors. Although T-ALL prognosis has significantly improved due to the development of intensive chemotherapeutic protocols, primary drug-resistant and relapsed patients still display a dismal outcome. In addition, lifelong irreversible late effects from conventional therapy are a growing problem for leukemia survivors. Therefore, novel targeted therapies are required to improve the prognosis of high-risk patients. The mechanistic target of rapamycin (mTOR) is the kinase subunit of two structurally and functionally distinct multiprotein complexes, which are referred to as mTOR complex 1 (mTORC1) and mTORC2. These two complexes regulate a variety of physiological cellular processes including protein, lipid, and nucleotide synthesis, as well as autophagy in response to external cues. However, mTOR activity is frequently deregulated in cancer, where it plays a key oncogenetic role driving tumor cell proliferation, survival, metabolic transformation, and metastatic potential. Promising preclinical studies using mTOR inhibitors have demonstrated efficacy in many human cancer types, including T-ALL. Here, we highlight our current knowledge of mTOR signaling and inhibitors in T-ALL, with an emphasis on emerging evidence of the superior efficacy of combinations consisting of mTOR inhibitors and either traditional or targeted therapeutics.

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Section: Discussionmentioning

confidence: 99%

Therapeutic Targeting of mTOR in T-Cell Acute Lymphoblastic Leukemia: An Update

Evangelisti

Chiarini

McCubrey

et al. 2018

IJMS

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“…Considering the instability of emulsion, chemical modifications need to be employed in order to improve ALM’s solubility or reduce the effective dose for further studies and clinical application. Nowadays, almost 30% of patients received Everolimus exhibits severe side effects, such as mouth sores, stomatitis, infection, mucositis and so on [35,36]. In addition, chronic rapamycin administration results in a diabetes-like syndrome due to hyperlipidemia, glucose intolerance, and reduced fat mass [37].…”

Section: Discussionmentioning

confidence: 99%

2-Oxonanonoidal Antibiotic Actinolactomycin Inhibits Cancer Progression by Suppressing HIF-1α

Cheng

Yang

et al. 2019

Cells

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HIF-1 serves as an important regulator in cell response to hypoxia. Due to its key role in promoting tumor survival and progression under hypoxia, HIF-1 has become a promising target of cancer therapy. Thus far, several HIF-1 inhibitors have been identified, most of which are from synthesized chemical compounds. Here, we report that ALM (ActinoLactoMycin), a compound extracted from metabolites of Streptomyces flavoretus, exhibits inhibitory effect on HIF-1α. Mechanistically, we found that ALM inhibited the translation of HIF-1α protein by suppressing mTOR signaling activity. Treatment with ALM induced cell apoptosis and growth inhibition of cancer cells both in vitro and in vivo in a HIF-1 dependent manner. More interestingly, low dose of ALM treatment enhanced the anti-tumor effect of Everolimus, an inhibitor of mTOR, suggesting its potential use in combination therapy of tumors, especially solid tumor patients. Thus, we identified a novel HIF-1α inhibitor from the metabolites of Streptomyces flavoretus, which shows promising anti-cancer potential.

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“…Molecules inhibiting specific components of different signaling pathways may cause hyperglycaemia. The mTOR pathway inhibitors (everolimus, sirolimus, and temsirolimus) used in breast cancer, advanced renal cell carcinoma, and neuroendocrine tumours (NETs) carry out their anticancer effect by inhibiting pathways normally involved in cell metabolism, proliferation, growth, and angiogenesis [84][85][86]. mTOR-inhibitors increase insulin-resistance and glycaemic levels in both diabetic and non-diabetic cancer patients [71,87] ( Table 1).…”

Section: Mtor Pathway Inhibitorsmentioning

confidence: 99%

Type 2 diabetes and cancer: problems and suggestions for best patient management

Milluzzo

Vigneri

Martorana

et al. 2020

Exploration of Medicine

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Diabetes and cancer are widespread worldwide and the number of subjects presenting both diseases increased over the years. The management of cancer patients having diabetes represents a challenge not only because of the complexity and heterogeneity of these pathologies but also for the lack of standardised clinical guidelines. The diagnosis of cancer is traumatizing and monopolizes the attention of both patients and caregivers. Thus, pre-existent or new-onset diabetes can be overshadowed thus increasing the risk for short- and long-term adverse events. Moreover, drugs used for each disease can interfere with the clinical course of the concomitant disease, making challenging the management of these patients. Over the years, this issue has become more relevant because of the increased patients’ life expectancy due to the improved efficacy of diabetes and cancer therapies. The purpose of this review is to highlight what is known and what should be taken into consideration to optimise the clinical management of patients with diabetes and cancer. Due to the complexity of these diseases, a multidisciplinary, shared approach, including all the protagonists involved, is necessary to improve patients’ quality of life and lifespan.

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Everolimus is a new anti-cancer molecule: Metabolic side effects as lipid disorders and hyperglycemia

Cited by 32 publications

References 8 publications

Therapeutic Targeting of mTOR in T-Cell Acute Lymphoblastic Leukemia: An Update

Therapeutic Targeting of mTOR in T-Cell Acute Lymphoblastic Leukemia: An Update

2-Oxonanonoidal Antibiotic Actinolactomycin Inhibits Cancer Progression by Suppressing HIF-1α

Type 2 diabetes and cancer: problems and suggestions for best patient management

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