The mammalian target of rapamycin (mTOR) pathway is critical for normal myeloid and lymphoid development and function, and hyperactivation of mTOR is a hallmark of many hematologic malignancies. The mTOR pathway is a key pathway for cellular processes including cell growth, proliferation and differentiation, as well as being involved in transmitting and integrating signals from the immune microenvironment, and regulating immune metabolism and function. Both the PI3K/Akt/mTOR pathway and the LKB1/AMPK/mTOR pathway have been identified as upstream signaling pathways for mTOR, positively and negatively regulating mTOR respectively.
Research investigating the use of rapamycin, the first mTOR inhibitor, and its analogs in hematologic malignancies has demonstrated their ability to induce apoptosis, cell cycle arrest and signal transduction inhibition, as well as impacting gene transcription and epigenetic regulation. For example, in patients with myelodysplastic syndromes (MDS), mTOR pathway activation has been observed in CD33+ cells and rapamycin has shown some efficacy in patients with advanced MDS. Everolimus has demonstrated single-agent activity in Hodgkin and non-Hodgkin lymphoma, and temsirolimus has demonstrated efficacy in both marginal zone lymphoma and diffuse large B-cell lymphoma. For multiple myeloma, aberrant expression of the PI3K/Akt/mTOR signaling pathway has been indicated, and evidence of everolimus and temsirolimus efficacy has been reported in clinical trials.
This Research Topic aims to collate research articles which contribute to our understanding of the mTOR pathway in relation to hematologic malignancies and how this can be leveraged to identify novel treatment approaches and improve existing treatment approaches.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
The mammalian target of rapamycin (mTOR) pathway is critical for normal myeloid and lymphoid development and function, and hyperactivation of mTOR is a hallmark of many hematologic malignancies. The mTOR pathway is a key pathway for cellular processes including cell growth, proliferation and differentiation, as well as being involved in transmitting and integrating signals from the immune microenvironment, and regulating immune metabolism and function. Both the PI3K/Akt/mTOR pathway and the LKB1/AMPK/mTOR pathway have been identified as upstream signaling pathways for mTOR, positively and negatively regulating mTOR respectively.
Research investigating the use of rapamycin, the first mTOR inhibitor, and its analogs in hematologic malignancies has demonstrated their ability to induce apoptosis, cell cycle arrest and signal transduction inhibition, as well as impacting gene transcription and epigenetic regulation. For example, in patients with myelodysplastic syndromes (MDS), mTOR pathway activation has been observed in CD33+ cells and rapamycin has shown some efficacy in patients with advanced MDS. Everolimus has demonstrated single-agent activity in Hodgkin and non-Hodgkin lymphoma, and temsirolimus has demonstrated efficacy in both marginal zone lymphoma and diffuse large B-cell lymphoma. For multiple myeloma, aberrant expression of the PI3K/Akt/mTOR signaling pathway has been indicated, and evidence of everolimus and temsirolimus efficacy has been reported in clinical trials.
This Research Topic aims to collate research articles which contribute to our understanding of the mTOR pathway in relation to hematologic malignancies and how this can be leveraged to identify novel treatment approaches and improve existing treatment approaches.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
