Emerging Roles for Mammalian Target of Rapamycin (mTOR) Complexes in Bladder Cancer Progression and Therapy

Jianya Huan, Petros Grivas, Jasmine Birch, Donna E. Hansel

Research output: Contribution to journalReview articlepeer-review

Abstract

The mammalian target of rapamycin (mTOR) pathway regulates important cellular functions. Aberrant activation of this pathway, either through upstream activation by growth factors, loss of inhibitory controls, or molecular alterations, can enhance cancer growth and progression. Bladder cancer shows high levels of mTOR activity in approximately 70% of urothelial carcinomas, suggesting a key role for this pathway in this cancer. mTOR signaling initiates through upstream activation of phosphatidylinositol 3 kinase (PI3K) and protein kinase B (AKT) and results in activation of either mTOR complex 1 (mTORC1) or mTOR complex 2 (mTORC2). While these complexes share several key protein components, unique differences in their complex composition dramatically alter the function and downstream cellular targets of mTOR activity. While significant work has gone into analysis of molecular alterations of the mTOR pathway in bladder cancer, this has not yielded significant benefit in mTOR-targeted therapy approaches in urothelial carcinoma to date. New discoveries regarding signaling convergence onto mTOR complexes in bladder cancer could yield unique insights the biology and targeting of this aggressive disease. In this review, we highlight the functional significance of mTOR signaling in urothelial carcinoma and its potential impact on future therapy implications.

Original languageEnglish (US)
Article number1555
JournalCancers
Volume14
Issue number6
DOIs
StatePublished - Mar 1 2022
Externally publishedYes

Keywords

  • Bladder cancer
  • Inhibitor
  • Invasion
  • MTOR
  • Progression
  • Targeted therapy
  • Urothelial carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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