Clinical activity of mammalian target of rapamycin inhibitors in solid tumors

Alvarado, Yesid; Mita, Monica; Vemulapalli, Sushma; Mahalingam, Devalingam; Mita, Alain C.

doi:10.1007/s11523-011-0178-5

Cited by 37 publications

(29 citation statements)

References 204 publications

(216 reference statements)

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“…mTOR is regulated by phosphoinositide-3-kinase (PI3K) [67]. The mTOR inhibitor sirolimus has been shown to inhibit lymphangiogenesis, and it has been successfully used as a treatment option for vascular anomalies in children [28,[68][69][70]. Advantages of sirolimus include oral administration without the need for a central line and more rapid…”

Section: Role Of Mtor Inhibitorsmentioning

confidence: 99%

Clinical Review: Management of Adult Kasabach-Merritt Syndrome Associated with Hemangiomas

Master¹,

Kallam²,

Eo³

et al. 2017

J Blood Disord Transfus

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Kasabach-Merritt syndrome (KMS) consists of a clinical trial of capillary hemangioma, thrombocytopenia and disseminated intravascular coagulation. KMS occurs most commonly in the pediatric population, and its occurrence in adults is rare. Specific guidelines or randomized clinical trials guiding clinical management of KMS in adult patients are lacking. This manuscript provides a comprehensive review of KMS and discusses recent advances in the medical management of KMS. We also propose a systematic therapeutic approach which would serve as a guide in the management of adult patients with KMS caused by hemangiomas.

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Section: Role Of Mtor Inhibitorsmentioning

confidence: 99%

Clinical Review: Management of Adult Kasabach-Merritt Syndrome Associated with Hemangiomas

Master¹,

Kallam²,

Eo³

et al. 2017

J Blood Disord Transfus

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“…This is the case for mTOR inhibitors, of which rapamycin (or sirolimus) is the prototype, used as a basis to develop several chemical derivatives or ‘rapalogues’, such as everolimus and temsirolimus, now proposed in the treatment of several types of solid tumors [54]. In addition to their multiple roles, mTOR inhibitors also have anti-angiogenic properties.…”

Section: Anti-angiogenic Treatments In Netsmentioning

confidence: 99%

Angiogenesis in Neuroendocrine Tumors: Therapeutic Applications

Scoazec

2012

Neuroendocrinology

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The considerable research efforts devoted to the understanding of the mechanisms of tumor angiogenesis have resulted in the development of targeted anti-angiogenic therapies and finally in their introduction in clinical practice. Neuroendocrine tumors (NETs), which are characterized by a high vascular supply and a strong expression of VEGF-A, one of the most potent pro-angiogenic factors, are an attractive indication for these new treatments. However, several lines of evidence show that the dense vascular networks associated with low-grade NETs are more likely to be a marker of differentiation than a marker of aggressiveness, as in other epithelial tumors. These observations form the basis for the so-called ‘neuroendocrine paradox’, according to which the most vascularized are the most differentiated and the less angiogenic NETs. This must be kept in mind when discussing the role of anti-angiogenic strategies in the treatment of NETs. Nevertheless, several targeted therapies, with direct or indirect anti-angiogenic properties, including anti-VEGF antibodies, tyrosine kinase inhibitors (sunitinib) and mTOR inhibitors (everolimus), have recently proven to be of clinical benefit. In addition, some drugs already used in NET treatment, such as somatostatin analogues and interferon-α, may also have anti-angiogenic properties. The main challenges for the next future are to validate biomarkers for the selection of patients and the prediction of their response to refine the indications of anti-angiogenic targeted therapies and to overcome the mechanisms of resistance, which explain the limited duration of action of most of these treatments.

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“…Nevertheless, rapamycin has limited bioavailability due to its poor aqueous solubility. In an effort to improve its pharmacokinetics, several rapamycin analogues, named rapalogs, have been developed, such as the mTOR inhibitors temsirolimus (CCI-779), everolimus (RAD001) and ridaforolimus (MK-8669/AP23573) [4,92,93]. Rapamycin and its derivates exhibit a safe toxicity profile, being the side effects skin rashes and mucositis dose-dependent [94].…”

Section: Rapamycin and Its Derivativesmentioning

confidence: 99%

Metformin and mTOR Inhibitors: Allies against Ovarian and Breast Cancers

Guimarães¹,

Tessarollo²,

Santos³

et al. 2017

J Carcinog Mutagen

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Cancer is one of the leading causes of death worldwide. Every year 8.2 million people die from the disease. In this context, breast and ovarian cancer are the most incidental among women. Elucidation of cell growth pathways and the observation that these pathways are altered in human cancer have encouraged the search for specific inhibitors. The phosphatidylinositol-3cinase (PI3K)/Protein kinase b (AKT)/Mammalian Target of Rapamycin (mTOR) is an important pathway involved in cell growth, tumorigenesis, cell invasion, and resistance to therapies. This pathway is often activated in breast and ovarian cancers and the deregulation of its signaling can contribute to tumor growth, angiogenesis and metastasis. Metformin is one of the most commonly prescribed antidiabetic drugs in the world whose anticancer effects, mediated by reduced mTOR signaling, have become notable. Therefore, this review provides an overview of signaling pathway PI3K/AKT/mTOR in the ovarian and breast cancers as well as for target therapies of mTOR signaling, with an emphasis on its mechanisms, clinical applicability and future perspectives.

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Clinical activity of mammalian target of rapamycin inhibitors in solid tumors

Cited by 37 publications

References 204 publications

Clinical Review: Management of Adult Kasabach-Merritt Syndrome Associated with Hemangiomas

Clinical Review: Management of Adult Kasabach-Merritt Syndrome Associated with Hemangiomas

Angiogenesis in Neuroendocrine Tumors: Therapeutic Applications

Metformin and mTOR Inhibitors: Allies against Ovarian and Breast Cancers

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