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Deciphering the PI3K-AKT-mTOR Signalling Pathway in Cancer: A Mechanistic Insight

Chetana C Galav1, Somali Sanyal2, Sukriti Singh2

  • 1Department of Biotechnology, Chhatrapati Shivaji Maharaj University, Maharashtra, India.

Current Topics in Medicinal Chemistry
|June 9, 2026
PubMed

Insights

The PI3K-AKT-mTOR pathway is crucial in cancer development. Inhibiting this pathway with targeted therapies and combination treatments offers new hope for effective cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The Phosphatidylinositol 3-kinase (PI3K)-AKT-mammalian Target of Rapamycin (mTOR) signaling pathway regulates fundamental cellular processes like growth, survival, and proliferation.
  • Dysregulation of the PI3K-AKT-mTOR pathway is implicated in the initiation and progression of numerous human cancers.

Purpose of the Study:

  • To review the mechanistic and structural aspects of the PI3K-AKT-mTOR pathway.
  • To explore the therapeutic potential of targeting this pathway in cancer treatment.
  • To discuss current and emerging therapeutic strategies, including combination therapies and overcoming resistance.

Main Methods:

  • Literature review of mechanistic and structural complexities of PI3K-AKT-mTOR pathway components.
  • Analysis of current therapeutic strategies targeting PI3K, AKT, and mTOR.
  • Examination of resistance mechanisms and novel therapeutic approaches.

Main Results:

  • Aberrant PI3K-AKT-mTOR signaling is linked to various cancers (breast, ovarian, gastric, lung, prostate, endometrial, laryngeal, hepatocellular carcinoma).
  • Small-molecule inhibitors and monoclonal antibodies are key therapeutic agents.
  • Combination therapies show promise in enhancing efficacy and overcoming resistance.

Conclusions:

  • Targeting the PI3K-AKT-mTOR pathway presents a significant therapeutic opportunity in oncology.
  • Understanding and overcoming resistance mechanisms is critical for improving patient outcomes.
  • This review provides insights into evolving trends in cancer treatment targeting this pathway.
Keywords:
.CancerPI3K-AKT-mTORdrug targetmonoclonal antibodiespathway inhibitionregulating cell growthsmall-molecule inhibitorstherapy

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