Therapeutic targeting of the mTOR-signalling pathway in cancer: benefits and limitations

Area of Science:

• Cellular Biology
• Molecular Biology
• Oncology

Background:

• The mammalian target of rapamycin (mTOR) is a central regulator of protein translation, cell growth, and metabolism.
• mTOR exists in two complexes, mTORC1 and mTORC2, with distinct functions and regulation.
• mTORC1 regulates cell growth, proliferation, and survival by responding to growth factors, nutrients, and stress signals, activating S6K1 and 4EBP1 for mRNA translation.

Purpose of the Study:

• To summarize the upstream regulators and downstream effectors of mTORC1 and mTORC2 pathways.
• To elucidate the role of mTOR signaling in cancer development and progression.
• To review the therapeutic potential and challenges of novel mTOR-targeting agents.

Main Methods:

• Review of scientific literature on mTOR signaling pathways.
• Analysis of the role of mTOR deregulation in various cancers.
• Evaluation of current and emerging therapeutic strategies targeting mTOR.

Main Results:

• mTORC1 is activated by growth factors, nutrients, and stress, controlling cell growth and activating translation factors.
• mTORC2 regulates the actin cytoskeleton and is less sensitive to nutrient/energy signals, activating PKC-α and Akt.
• mTOR pathway deregulation, including PI3K/PTEN/Akt alterations and overexpression of downstream targets, is prevalent in cancer.

Conclusions:

• The mTOR pathway is critically involved in cancer pathogenesis due to frequent alterations in its components.
• mTOR represents a significant therapeutic target for various types of cancer.
• Further research into mTOR inhibitors is crucial for developing effective cancer treatments, addressing potential issues and challenges.