Impact of Lifestyle Interventions to Inhibit AKT/mTOR Pathway in Breast Cancer

A BSTRACT Breast cancer remains a major global health concern and is the second leading cause of cancer-related deaths among women in developed nations. Its pathogenesis is influenced by a range of factors, including population lifestyle, demographics, hormonal influences (both endogenous and exogenous), as well as physiological, genetic, and breast-specific characteristics. A key molecular pathway implicated in breast cancer is the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway, which regulates crucial cellular processes such as proliferation, survival, invasion, migration, apoptosis, glucose metabolism, and DNA repair. A growing collection of evidence highlights the impact of lifestyle on disease-related outcomes. Unhealthy lifestyles with low levels of physical activity result in overweight and obesity, which appear to have a negative impact on breast cancer, and therefore, increase the risk of recurrence and death in all subtypes of breast cancer. The mechanisms underlying the effects of exercise and dietary changes on breast carcinogenesis are not clear. In this review, experimental evidence suggests that lifestyle modification induces PI3K/Akt/mTOR signaling pathway inhibition and slows down the breast cancer cell growth through decreasing AMP-activated protein kinase (AMPK) pathway. Yet, decreased AMPK activation brought on by calorie restriction and exercise, combined with decreased insulin and insulin-like growth factor-1 levels, results in less inflammation (lower tumor necrosis factor-α and interleukin-6), reduced leptin and adipokine levels (from fat loss), and lower stress hormone (cortisol) levels. These biological effects contribute to the inhibition of the Akt/mTOR pathway, which is associated with improved cancer-related outcomes.