Exercise and Regulation of PI3K/Akt/mTOR and AMPK  Pathways in Cancer: Molecular Mechanisms and Therapeutic  Implications: A Narrative Review

Abeer Issa Mohammed; Ochilova Gulrux Saidovna; Davron Makhmudov; Narkulova Sokhiba; Istamov Mirmukhsinjon Bakhodirovich; Shoista Sultonbekovna; Qobilov Odiljon Rustamovich; Niyozova Shaxnoza Xamoydinovna; Izrailbekova Kamila Shavkatovna; Achilova Ozoda Farkhodovna; Berdikulova Nigina Mirsoliyevna; Ergasheva Zilolaxon Xasanboy Qizi; Azim Akbarzadehkhayavi; Mohsen Mir

doi:10.31557/apjcc.2026.11.3.467-476

Authors

Abeer Issa Mohammed Al-Manara College for Medical Sciences, University of Manara, Iraq, Advanced Medical and Dental Institute, University Sains Malaysia, Kepala Batas, Pulau Penang, Malaysia.
Ochilova Gulrux Saidovna Department of Clinical Pharmacology, Bukhara State Medical Institute named after Abu Ali ibn Sino, Bukhara, Uzbekistan.
Davron Makhmudov Department of Children’s Infectious Diseases, Tashkent Pediatric Medical Institute, Tashkent, Uzbekistan.
Narkulova Sokhiba Department of Obstetrics and Gynecology N3, Samarkand State Medical University, Samarkand, Uzbekistan.
Istamov Mirmukhsinjon Bakhodirovich Department of Psychiatry, Narcology and Medical Psychology, Bukhara State Medical Institute named after Abu Ali ibn Sino, Bukhara Uzbekistan.
Shoista Sultonbekovna 6Department of Obstetrics and Gynecology No. 1, Faculty of Pediatrics, Andijan State Medical Institute, Uzbekistan.
Qobilov Odiljon Rustamovich Department of Oncology, Pediatric Oncology, and Palliative Care, Tashkent State Medical University, Tashkent, Uzbekistan.
Niyozova Shaxnoza Xamoydinovna Department of Oncology, Clinical Oncology, Oncohematology, and Radiation Oncology, Tashkent State Medical University, Tashkent, Uzbekistan.
Izrailbekova Kamila Shavkatovna Department of Republican Oncology Center, Medical Oncologist (Chemotherapist), Tashkent, Uzbekistan.
Achilova Ozoda Farkhodovna Department of Japanese Philology, Faculty of Oriental Languages, Samarkand State Institute of Foreign Languages, Uzbekistan.
Berdikulova Nigina Mirsoliyevna Department of Japanese Philology, Faculty of Oriental Languages, Samarkand State Institute of Foreign Languages, Uzbekistan.
Ergasheva Zilolaxon Xasanboy Qizi Department of Food Technology and Engineering, Faculty of Food Technology and Management, International Institute of Food Technology and Engineering, Uzbekistan.
Azim Akbarzadehkhayavi Professor of Institute Pasteur of Iran in Department of Nanobiotechnology, Tehran, Iran.
Mohsen Mir Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

DOI:

https://doi.org/10.31557/apjcc.2026.11.3.467-476

Keywords:

Keywords: Exercise, PI3K/Akt/mTOR, AMPK, Cancer, Insulin sensitivity, Autophagy

Abstract

Overview: Dysregulation of the PI3K/Akt/mTOR and AMPK pathways is central to cancer development, driving uncontrolled cell growth, metabolic disturbances, and resistance to cell death and therapy. Exercise has emerged as an effective non-drug strategy that can modify these pathways and influence tumor-related cellular processes.

Methods: This review compiles evidence from 2015 to 2025 on how exercise impacts PI3K/Akt/mTOR and AMPK signaling in cancer.

Results: Findings show that exercise activates AMPK, an energy sensor that boosts glucose uptake, insulin sensitivity, autophagy, and mitochondrial biogenesis. Through AMPK activation, exercise reduces anabolic signaling and excessive protein synthesis, which often promotes tumor growth, while supporting healthier metabolism. At the same time, exercise inhibits the PI3K/Akt/mTOR pathway, reducing cell proliferation, affecting growth factors like insulin and IGF-1, and restoring metabolic balance across tissues. These combined effects improve cellular stability, lessen tumor-promoting mechanisms, and may enhance responsiveness to cancer treatments, making exercise a valuable complement for cancer prevention and therapy. Most current insights come from preclinical studies or epidemiological data, with few clinical trials examining exercise-induced molecular changes in human tumors.

Conclusion: More research is needed to identify optimal exercise regimens, understand pathway-specific effects, and evaluate their clinical relevance to better incorporate exercise into personalized cancer care.