Abstract
Despite the endeavors and maneuvers in cancer treatment, drug resistance and toxicities have become a significant obstacle these days. Diverseness among the patients and tumor and the multifaceted nature of cancer to circumvent therapies make it more challenging. Adenosine monophosphate-activated protein kinase (AMPK) is a significant biosensor and it negatively regulates cancer growth by inhibiting the mechanistic target of rapamycin (mTOR) signaling cascade, which is responsible for cell growth and proliferation. These two critical regulators of growth are often found deregulated in human cancers. They act by triggering the AMPK pathway, thereby inducing mTOR inhibition leading to dephosphorylation of its downstream regulators S6K1 and 4EBP1, with two key regulators TSC2 and RHEB. Drugs like biguanides, Aspirin, resveratrol, quercetin, and some natural products were found to decrease cancer incidence by this cognate pathway. This pathway drew more attention for better strategies to enhance the treatment efficacy, but adequate evidence in this field is still lacking. Repurposing existing drugs with multimodal actions and fewer toxicities could be considered for newer therapies. Combined effects of an AMPK activator drug with an mTOR inhibitor when used in conjunction or a new drug developed with the above dual properties could be a promising strategy in this sector. Thus, scouting the significance of this pathway and combination therapies in a more personalized manner would be indeed a turning point for future investigations.
Keywords: Adenosine monophosphate-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR) inhibitor, combination therapies, drug repurposing, cancer drug resistance, non-cancerous medications.
Graphical Abstract
23