Targeting protein synthesis pathways in MYC-amplified medulloblastoma DOI Creative Commons
Devendra Kumar, Ranjana Kanchan, Nagendra K. Chaturvedi

et al.

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 8, 2025

Abstract MYC is one of the most deregulated oncogenic transcription factors in human cancers. amplification/or overexpression common Group 3 medulloblastoma and positively associated with poor prognosis. known to regulate major components protein synthesis (translation) machinery, leading promoted rates tumorigenesis. MTOR signaling-driven widespread various cancers, including medulloblastoma, which can promote stabilization MYC. Indeed, our previous studies demonstrate that key mTOR signaling targets, are overexpressed activated MYC-amplified confirming MYC-dependent addiction enhanced medulloblastoma. Further, targeting this pathway combined inhibition translation by small-molecule inhibitors, demonstrates preclinical synergistic anti-tumor potential against MYC-driven vitro vivo. Thus, inhibiting indirectly pathways together may present a highly appropriate strategy for treating other MYC-addicted Evidence strongly proposes MYC/mTOR-driven tumorigenic predominantly control translational machinery elicit cooperative effects on increased cell proliferation, cycle progression, genome dysregulation as mechanism cancer initiation. Several small molecule inhibitors have been developed used clinically immunosuppressants chemotherapy multiple Only few them investigated treatments pediatric tumors. This review explores concurrent Based existing evidence, produces functional synergy could be basis effective therapies

Language: Английский

Targeting protein synthesis pathways in MYC-amplified medulloblastoma DOI Creative Commons
Devendra Kumar, Ranjana Kanchan, Nagendra K. Chaturvedi

et al.

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 8, 2025

Abstract MYC is one of the most deregulated oncogenic transcription factors in human cancers. amplification/or overexpression common Group 3 medulloblastoma and positively associated with poor prognosis. known to regulate major components protein synthesis (translation) machinery, leading promoted rates tumorigenesis. MTOR signaling-driven widespread various cancers, including medulloblastoma, which can promote stabilization MYC. Indeed, our previous studies demonstrate that key mTOR signaling targets, are overexpressed activated MYC-amplified confirming MYC-dependent addiction enhanced medulloblastoma. Further, targeting this pathway combined inhibition translation by small-molecule inhibitors, demonstrates preclinical synergistic anti-tumor potential against MYC-driven vitro vivo. Thus, inhibiting indirectly pathways together may present a highly appropriate strategy for treating other MYC-addicted Evidence strongly proposes MYC/mTOR-driven tumorigenic predominantly control translational machinery elicit cooperative effects on increased cell proliferation, cycle progression, genome dysregulation as mechanism cancer initiation. Several small molecule inhibitors have been developed used clinically immunosuppressants chemotherapy multiple Only few them investigated treatments pediatric tumors. This review explores concurrent Based existing evidence, produces functional synergy could be basis effective therapies

Language: Английский

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