Muscle atrophy is a hallmark of cancer cachexia, a complex multifactorial wasting disease highly associated with mortality. In recent years, we have learned a lot about the protective effects of exercise during cancer. Resistance exercise is now recognized as a safe and feasible tool to counteract muscle wasting and cancer cachexia, yet little is known about the mechanism by which exercise exert protection against cancer-induced muscle wasting. In healthy humans and animals, resistance exercise promotes the activation of mTORC1 axis, which is associated with skeletal muscle hypertrophy to promote muscle growth. In this study, researchers proposed a cause-and-effect experimental approach to determine the role of hypertrophy signaling on anti-atrophy effects of exercise during cancer cachexia. They found that by inducing attenuated myofiber atrophy independent of hypertrophy mTORC1’s signaling activation, resistance exercise prevents muscle atrophy during cancer by reducing inflammation, oxidative damage, and atrogin-1 expression.