mTOR signalling and cellular metabolism are mutual determinants in cancer

Area of Science:

• Biochemistry
• Oncology
• Cell Biology

Background:

• Oncogenic signaling pathways and metabolic reprogramming are critical hallmarks of cancer.
• The mechanistic target of rapamycin (mTOR) pathway is frequently hyperactivated in various cancers, regulating cell growth and metabolism.
• mTOR signaling influences multiple metabolic pathways, including amino acid, glucose, nucleotide, fatty acid, and lipid metabolism.

Purpose of the Study:

• To review the intricate relationship between mTOR signaling and cancer cell metabolism.
• To elucidate how mTOR signaling rewires cancer metabolism and how metabolic changes sustain mTOR activity and tumorigenicity.
• To explore the potential of targeting the interdependence of mTOR signaling and metabolism for cancer therapy.

Main Methods:

• Literature review and synthesis of existing research on mTOR signaling and cancer metabolism.
• Analysis of how mTOR pathway activation impacts key metabolic pathways in cancer cells.
• Discussion of metabolic inputs that activate mTOR signaling.
• Evaluation of current therapeutic strategies targeting cancer metabolism and mTOR inhibitors.

Main Results:

• mTOR signaling extensively reprograms cancer cell metabolism to support rapid growth and proliferation.
• Metabolic alterations, such as amino acid availability, can feedback to activate and sustain mTOR signaling.
• The bidirectional crosstalk between mTOR and metabolism is crucial for maintaining cancer cell viability and tumorigenicity.
• Current therapies targeting either mTOR or metabolism alone show limited efficacy.

Conclusions:

• The interdependence of mTOR signaling and cancer metabolism presents a promising therapeutic vulnerability.
• Combination strategies that simultaneously target mTOR signaling and metabolic pathways may overcome therapeutic resistance.
• Exploiting this metabolic-signaling axis holds potential for developing more effective cancer treatments.