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Targeting cancer via ribosome biogenesis: the cachexia perspective

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Abstract

Cancer cachexia afflicts many advanced cancer patients with many progressing to death. While there have been many advancements in understanding the molecular mechanisms that contribute to the development of cancer cachexia, substantial gaps still exist. Chemotherapy drugs often target ribosome biogenesis to slow or blunt tumor cell growth and proliferation. Some of the most frequent side-effects of chemotherapy are loss of skeletal muscle mass, muscular strength and an increase in fatigue. Given that ribosome biogenesis has emerged as a main mechanism regulating muscle hypertrophy, and more recently, also implicated in muscle atrophy, we propose that some chemotherapy drugs can cause further muscle wasting via its effect on skeletal muscle cells. Many chemotherapy drugs, including the most prescribed drugs such as doxorubicin and cisplatin, affect ribosomal DNA transcription, or other pathways related to ribosome biogenesis. Furthermore, middle-aged and older individuals are the most affected population with cancer, and advanced cancer patients often show reduced levels of physical inactivity. Thus, aging and inactivity can themselves affect muscle ribosome biogenesis, which can further worsen the effect of chemotherapy on skeletal muscle ribosome biogenesis and, ultimately, muscle mass and function. We propose that chemotherapy can accelerate the onset or worsen cancer cachexia via its inhibitory effects on skeletal muscle ribosome biogenesis. We end our review by providing recommendations that could be used to ameliorate the negative effects of chemotherapy on skeletal muscle ribosome biogenesis.

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  1. College of Health Sciences, University of Kentucky, Lexington, KY, USA

    Vandré Casagrande Figueiredo

  2. Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY, USA

    John J. McCarthy

  3. Center for Muscle Biology, University of Kentucky, Lexington, KY, USA

    Vandré Casagrande Figueiredo & John J. McCarthy

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Figueiredo, V.C., McCarthy, J.J. Targeting cancer via ribosome biogenesis: the cachexia perspective. Cell. Mol. Life Sci. 78, 5775–5787 (2021). https://doi.org/10.1007/s00018-021-03888-6

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