The LKB1-AMPK pathway plays a critical role in tumor suppression by linking cell metabolism to growth control and cell polarity. LKB1, a serine/threonine kinase, activates AMPK, a central metabolic sensor, which regulates lipid, cholesterol, and glucose metabolism. This pathway is also involved in cell polarity, and its disruption is implicated in carcinogenesis. LKB1 is a master kinase that activates AMPK and other kinases, including the MARK/Par-1 family, which are conserved across eukaryotes. LKB1 is frequently mutated in sporadic lung cancer and cervical carcinomas, making it a key target for cancer therapy. The LKB1-AMPK-mTORC1 pathway acts as a metabolic checkpoint, inhibiting tumor growth by suppressing mTORC1 activity. AMPK also regulates other growth regulators, such as p53 and the SIRT1 pathway, and influences cell polarity through various substrates. The pathway is involved in the regulation of glucose and lipid metabolism, and its dysregulation is associated with tumorigenesis. AMPK agonists, such as metformin, have shown promise as cancer therapeutics due to their ability to inhibit tumor growth and suppress mTORC1 signaling. Rapamycin analogs are also being explored for the treatment of LKB1-deficient tumors. The LKB1-AMPK pathway is a key target for cancer therapy, and further research is needed to fully understand its role in tumor suppression and to develop effective treatments.The LKB1-AMPK pathway plays a critical role in tumor suppression by linking cell metabolism to growth control and cell polarity. LKB1, a serine/threonine kinase, activates AMPK, a central metabolic sensor, which regulates lipid, cholesterol, and glucose metabolism. This pathway is also involved in cell polarity, and its disruption is implicated in carcinogenesis. LKB1 is a master kinase that activates AMPK and other kinases, including the MARK/Par-1 family, which are conserved across eukaryotes. LKB1 is frequently mutated in sporadic lung cancer and cervical carcinomas, making it a key target for cancer therapy. The LKB1-AMPK-mTORC1 pathway acts as a metabolic checkpoint, inhibiting tumor growth by suppressing mTORC1 activity. AMPK also regulates other growth regulators, such as p53 and the SIRT1 pathway, and influences cell polarity through various substrates. The pathway is involved in the regulation of glucose and lipid metabolism, and its dysregulation is associated with tumorigenesis. AMPK agonists, such as metformin, have shown promise as cancer therapeutics due to their ability to inhibit tumor growth and suppress mTORC1 signaling. Rapamycin analogs are also being explored for the treatment of LKB1-deficient tumors. The LKB1-AMPK pathway is a key target for cancer therapy, and further research is needed to fully understand its role in tumor suppression and to develop effective treatments.