Targeting the Activin Receptor Signaling to Counteract the Multi-Systemic Complications of Cancer and Its Treatments
Hulmi, J. J., Nissinen, T. A., Penna, F., & Bonetto, A. (2021). Targeting the Activin Receptor Signaling to Counteract the Multi-Systemic Complications of Cancer and Its Treatments. Cells, 10(3), Article 516. https://doi.org/10.3390/cells10030516
© 2021 the Authors
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. ...
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- Liikuntatieteiden tiedekunta 
Related funder(s)Academy of Finland
Funding program(s)Academy Research Fellow, AoF
Additional information about fundingThis review received no external funding but was supported by the Faculty of Sport and Health Sciences at University of Jyväskylä, the Department of Clinical and Biological Sciences at University of Turin and the Department of Surgery at Indiana University. The research leading to the results presented here also received funding from the Academy of Finland (grant No. 275922 to J.J.H.), Cancer Society of Finland (to J.J.H.), Jenny and Antti Wihuri as well as Ellen and Artturi Nyyssönen Foundations (to T.A.N.), AIRC (under IG 2018-ID. 21963 project to F.P.) and American Cancer Society (Research Scholar Grant 132013-RSG-18-010-01-CCG to A.B.). ...
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Blocking Activin Receptor Ligands Is Not Sufficient to Rescue Cancer-Associated Gut Microbiota : A Role for Gut Microbial Flagellin in Colorectal Cancer and Cachexia? Pekkala, Satu; Keskitalo, Anniina; Kettunen, Emilia; Lensu, Sanna; Nykänen, Noora; Kuopio, Teijo; Ritvos, Olli; Hentilä, Jaakko; Nissinen, Tuuli A.; Hulmi, Juha J. (MDPI AG, 2019)Colorectal cancer (CRC) and cachexia are associated with the gut microbiota and microbial surface molecules. We characterized the CRC-associated microbiota and investigated whether cachexia affects the microbiota composition. ...
Treating cachexia using soluble ACVR2B improves survival, alters mTOR localization, and attenuates liver and spleen responses Nissinen, Tuuli; Hentilä, Jaakko; Penna, Fabio; Lampinen, Anita; Lautaoja, Juulia; Fachada, Vasco; Holopainen, Tanja; Ritvos, Olli; Kivelä, Riikka; Hulmi, Juha (Wiley, 2018)Background Cancer cachexia increases morbidity and mortality, and blocking of activin receptor ligands has improved survival in experimental cancer. However, the underlying mechanisms have not yet been fully uncovered. ...
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Prevention of chemotherapy-induced cachexia by ACVR2B ligand blocking has different effects on heart and skeletal muscle Hulmi, Juha; Nissinen, Tuuli; Räsänen, Markus; Degerman, Joni; Lautaoja, Juulia; Hemanthakumar, Karthik Amudhala; Backman, Janne T.; Ritvos, Olli; Silvennoinen, Mika; Kivelä, Riikka (Wiley, 2018)Background Toxicity of chemotherapy on skeletal muscles and the heart may significantly contribute to cancer cachexia, mortality, and decreased quality of life. Doxorubicin (DOX) is an effective cytostatic agent, which ...
Muscle and serum metabolomes are dysregulated in colon-26 tumor-bearing mice despite amelioration of cachexia with activin receptor type 2B ligand blockade Lautaoja, Juulia; Lalowski, Maciej; Nissinen, Tuuli; Hentilä, Jaakko; Shi, Yi; Ritvos, Olli; Cheng, Sulin; Hulmi, Juha (American Physiological Society, 2019)Cancer-associated cachexia reduces survival, which has been attenuated by blocking the activin receptor type 2B (ACVR2B) ligands in mice. The purpose of this study was to unravel the underlying physiology and novel cachexia ...