AMP‑activated protein kinase (AMPK) and mechanistic target of rapamycin complexes (mTORCs; mTORC1 and mTORC2) have critical functions in controlling tumor cell metabolism, reciprocally affecting the anabolic and catabolic pathways that control cell growth, proliferation and survival. AMPK serves as a key energy sensor, activated in response to low cellular energy levels, while the action of mTORCs becomes evident under conditions with high nutrient and growth factors. The dysregulation of these cascades is notably detected in a number of types of cancer, where reduced AMPK activity and unrestrained mTOR signaling pathways accelerate metabolic shifts that support carcinogenesis. The connection between AMPK and mTOR is significant. AMPK plays a role in hindering mTOR signaling, thus diminishing protein biosynthesis and stimulating autophagy. This strengthens cellular homeostasis, progression and survival during severe metabolic distress. Nevertheless, the function of AMPK in tumors is multifaceted. At the same time, it commonly functions as a tumor suppressor; evidence suggests that in specific environments, AMPK may stimulate tumor development by supporting the survival of tumor cells under adverse conditions, such as metabolic deprivation. This dualism highlights that the therapeutic targeting of AMPK/mTOR signaling pathways needs to be addressed carefully, as the consequences may vary, depending on the specific cancer microenvironment and nutrient state. The present review summarizes evidence from the literature in an aim to shed light onto the complex balance of the actions, regulation and critical role of AMPK and mTORCs in cancer cell metabolism. The present review aimed to provide insight that may lead to the development of novel targeted therapies that diminish the threat of unfavorable consequences associated with modified metabolic control.

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