Characterization of mTOR Activity and Metabolic Profile in Pediatric Rhabdomyosarcoma

Felkai, Luca; Krencz, Ildikó; Kiss, Dorottya; Nagy, Noémi; Petővári, Gábor; Dankó, Titanilla; Micsik, Tamás; Khoór, András; Tornóczky, Tamás; Szepes, Zoltán; Sebestyén, Anna; Csóka, Monika

doi:10.3390/cancers12071947

Cited by 11 publications

(11 citation statements)

References 49 publications

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“…in metastatic NSCLC) [ 105 – 107 ]. Other studies also call the attention to metabolism-targeting agents in combinations, which highlights that these could potentially enhance the impact of sensitizing strategies and accordingly, mTOR inhibitors could inhibit tumor progression as having a complex modifying role on metabolism [ 108 – 113 ].…”

Section: Metabolic Therapymentioning

confidence: 99%

Hypoxia Signaling in Cancer: From Basics to Clinical Practice

Sebestyén

Kopper

Dankó

et al. 2021

Pathol. Oncol. Res.

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Cancer hypoxia, recognized as one of the most important hallmarks of cancer, affects gene expression, metabolism and ultimately tumor biology-related processes. Major causes of cancer hypoxia are deficient or inappropriate vascularization and systemic hypoxia of the patient (frequently induced by anemia), leading to a unique form of genetic reprogramming by hypoxia induced transcription factors (HIF). However, constitutive activation of oncogene-driven signaling pathways may also activate hypoxia signaling independently of oxygen supply. The consequences of HIF activation in tumors are the angiogenic phenotype, a novel metabolic profile and the immunosuppressive microenvironment. Cancer hypoxia and the induced adaptation mechanisms are two of the major causes of therapy resistance. Accordingly, it seems inevitable to combine various therapeutic modalities of cancer patients by existing anti-hypoxic agents such as anti-angiogenics, anti-anemia therapies or specific signaling pathway inhibitors. It is evident that there is an unmet need in cancer patients to develop targeted therapies of hypoxia to improve efficacies of various anti-cancer therapeutic modalities. The case has been opened recently due to the approval of the first-in-class HIF2α inhibitor.

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Section: Metabolic Therapymentioning

confidence: 99%

Hypoxia Signaling in Cancer: From Basics to Clinical Practice

Sebestyén

Kopper

Dankó

et al. 2021

Pathol. Oncol. Res.

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“…Activation of the phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt)-mammalian target of rapamycin (mTOR) pathway is proposed to be implicated in the development of a variety of sarcomas [ 96 , 97 , 98 ]. There is emerging data indicating the possible involvement of the mTOR pathway in DSRCT.…”

Section: Treatmentmentioning

confidence: 99%

Desmoplastic Small Round Cell Tumor: A Review of Main Molecular Abnormalities and Emerging Therapy

Mello

Campos

Santos

et al. 2021

Cancers

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Desmoplastic small round cell tumor (DSRCT) is an extremely rare, aggressive sarcoma affecting adolescents and young adults with male predominance. Generally, it originates from the serosal surface of the abdominal cavity. The hallmark characteristic of DSRCT is the EWSR1–WT1 gene fusion. This translocation up-regulates the expression of PDGFRα, VEGF and other proteins related to tumor and vascular cell proliferation. Current management of DSRCT includes a combination of chemotherapy, radiation and aggressive cytoreductive surgery plus intra-peritoneal hyperthermic chemotherapy (HIPEC). Despite advances in multimodal therapy, outcomes remain poor since the majority of patients present disease recurrence and die within three years. The dismal survival makes DSRCT an orphan disease with an urgent need for new drugs. The treatment of advanced and recurrent disease with tyrosine kinase inhibitors, such as pazopanib, sunitinib, and mTOR inhibitors was evaluated by small trials. Recent studies using comprehensive molecular profiling of DSRCT identified potential therapeutic targets. In this review, we aim to describe the current studies conducted to better understand DSRCT biology and to explore the new therapeutic strategies under investigation in preclinical models and in early phase clinical trials.

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“…Activation of the phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt)-mammalian target of rapamycin (mTOR) pathway is proposed to be implicated in the development of a variety of sarcomas [96][96] , [97] , [98]. Also, there is emerging data indicating possible involvement of mTOR pathway in DSRCT.…”

Section: Targeting Pi3k/akt/mtor Pathwaymentioning

confidence: 99%

Desmoplastic Small Round Cell Tumor: A Review of Main Molecular Abnormalities and Emerging Therapy

Mello¹,

Campos²,

Santos³

et al. 2020

Preprint

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Desmoplastic small round cell tumor (DSRCT) is an extremely rare, aggressive sarcoma affecting adolescents and young adults with male predominance. Generally, it originates from serosal surface of abdominal cavity. The hallmark characteristic of DSRCT is the EWSR1-WT1 gene fusion. This translocation up-regulates the expression of PDGFRα, VEGF and other proteins related to tumor and vascular cell proliferation. Current management of DSRCT includes a combination of chemotherapy, radiation and aggressive cytoreductive surgery plus intra-peritoneal hyperthermic chemotherapy (HIPEC). Despite advances in multimodal therapy, outcomes remain poor since the majority of patients present disease recurrence and die within 3 years. The dismal survival makes DSRCT an orphan disease with urgent need of new drugs. The treatment of advanced and recurrent disease with tyrosine kinase inhibitors, such as pazopanib, sunitinib, and mTOR inhibitors have been evaluated in small studies. Recent works using comprehensive molecular profiling of DSRCT identified potential therapeutic targets. In this review, we aim to describe the current studies conducted to better understand DSRCT biology and to explore the new therapeutic strategies under investigation in preclinical models and in early phase clinical trials.

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Characterization of mTOR Activity and Metabolic Profile in Pediatric Rhabdomyosarcoma

Cited by 11 publications

References 49 publications

Hypoxia Signaling in Cancer: From Basics to Clinical Practice

Hypoxia Signaling in Cancer: From Basics to Clinical Practice

Desmoplastic Small Round Cell Tumor: A Review of Main Molecular Abnormalities and Emerging Therapy

Desmoplastic Small Round Cell Tumor: A Review of Main Molecular Abnormalities and Emerging Therapy

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