Faculty of Sport and Health Sciences, NeuroMuscular Research Center, University of Jyväskylä, 40014 Jyväskylä, Finland.
Department of Clinical and Biological Sciences, University of Turin, 10125 Turin, Italy.
Cells. 2021 Feb 28;10(3):516. doi: 10.3390/cells10030516.
Muscle wasting, i.e., cachexia, frequently occurs in cancer and associates with poor prognosis and increased morbidity and mortality. Anticancer treatments have also been shown to contribute to sustainment or exacerbation of cachexia, thus affecting quality of life and overall survival in cancer patients. Pre-clinical studies have shown that blocking activin receptor type 2 (ACVR2) or its ligands and their downstream signaling can preserve muscle mass in rodents bearing experimental cancers, as well as in chemotherapy-treated animals. In tumor-bearing mice, the prevention of skeletal and respiratory muscle wasting was also associated with improved survival. However, the definitive proof that improved survival directly results from muscle preservation following blockade of ACVR2 signaling is still lacking, especially considering that concurrent beneficial effects in organs other than skeletal muscle have also been described in the presence of cancer or following chemotherapy treatments paired with counteraction of ACVR2 signaling. Hence, here, we aim to provide an up-to-date literature review on the multifaceted anti-cachectic effects of ACVR2 blockade in preclinical models of cancer, as well as in combination with anticancer treatments.
肌肉减少症，即恶病质，常发生于癌症患者，与不良预后、发病率和死亡率增加有关。抗癌治疗也被证明会导致恶病质的持续或恶化，从而影响癌症患者的生活质量和总体生存率。临床前研究表明，阻断激活素受体型 2（ACVR2）或其配体及其下游信号通路可以维持实验性癌症荷瘤鼠以及接受化疗治疗动物的肌肉质量。在荷瘤小鼠中，预防骨骼和呼吸肌消耗也与生存率的提高相关。然而，阻断 ACVR2 信号通路后肌肉保存可直接导致生存率提高的确切证据仍缺乏，特别是考虑到在存在癌症或在与 ACVR2 信号通路拮抗作用相关的化疗治疗后，除了骨骼肌之外的其他器官也同时具有有益作用。因此，在这里，我们旨在提供关于 ACVR2 阻断在癌症的临床前模型中的多方面抗恶病质作用以及与抗癌治疗联合应用的最新文献综述。
