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INNOSC Theranostics and
Pharmacological Sciences Anabolic agents in cancer cachexia

prostate tumors. Moreover, breast, renal, and urothelial kinases, which can phosphorylate the beta-2 adrenergic
cancers have high androgen receptor expression. However, receptor at multiple sites, deactivating it through insulin.
androgen receptor expression varies across different tumor Insulin-like growth factor (IGF-1) can also phosphorylate
types, with an approximate expression of 25 – 75% in and deactivate the receptor. In addition, eukaryotic
breast cancer. initiation factor 2B activates the beta-2 adrenergic receptor,
The expression of the androgen receptor is not whereas arrestin is involved in decreasing receptor
homogeneous for all tumors of the same type. Some activation and signaling. There may be other mechanisms
patients are androgen receptor-positive, whereas others of action for beta-2 adrenergic agonists in the skeletal
are not for a given tumor type. Breast cancer can be muscle and interactions with other pathways, but these
androgen receptor-positive or androgen receptor-negative, have yet to be elucidated. A book chapter published nearly
25
suggesting that the same type of cancer may have tumors two decades ago suggested that IGF-II could mediate
that are proliferative to androgens, whereas others are beta-2 adrenergic agonist activation in skeletal muscle.
not responsive. Individual testing of biopsy samples 8. Conclusion
from the tumor with immunohistochemistry could help
with this approach. For androgen receptor-negative Testosterone, anabolic steroids, and albuterol are promising
tumors, androgens may be used. In contrast, for androgen options to reduce the loss of ~5 million lives over the next
receptor-positive tumors, non-androgenic anabolics such 10 – 15 years. These agents, though not extensively studied
as albuterol could be more appropriate. in cancer cachexia, offer hope if used properly and for
sufficient duration.
7. Discussion

Cancer cachexia affects many cancer patients, and Acknowledgments
developing new drugs for this condition is a long and The US National Institute of Health/ National Institute of
costly process, with an estimated 5 million cancer patients Aging for their kind support of the Albuterol Project.
potentially dying in the meantime. Repurposing already
approved anabolic agents, such as testosterone and Funding
anabolic steroids, could substantially reduce the mortality None.
rate of cancer cachexia.
Conflict of interest
One potential treatment that required rigorous clinical
trials in androgen receptor-positive cancers is albuterol. The author declares he has no competing interests.
The rationale for using albuterol in these cancers is that
androgens can stimulate tumor proliferation. Uc et al. Author contributions
23
previously reported in Parkinson’s patients that albuterol This is a single-authored article.
23
was anabolic to skeletal muscle. In a previous study, a
5.3% increase in lower limb muscle mass (quadriceps Ethics approval and consent to participate
femoris) and a 9.5% increase in whole body lean body mass Approval for Albuterol study was obtained from the local
were observed after 14 weeks of albuterol administration ethics commitee.
(16 mg/day). Lambert et al. (unpublished data) observed
a 90% increase in skeletal muscle protein synthesis (in Consent for publication
the vastus lateralis skeletal muscle) as a result of 16 mg/ Not applicable.
day albuterol administration for 10 days in healthy elderly
individuals. Future clinical trials involving albuterol in Availability of data
androgen receptor-positive cancer patients are warranted
to help attenuate and mitigate death from cancer cachexia. Data are available from the corresponding author upon
The mechanism of action of albuterol is likely due to the reasonable request.
increase in cAMP intracellularly through stimulation References
of the beta-2 adrenergic receptor, thereby inducing the
phosphorylation of various kinases within the skeletal 1. Von Haehling S, Anker MS, Anker SD. Prevalence and
muscle cell. The exact mechanism by which albuterol clinical impact of cachexia in chronic illness in Europe,
24
stimulates skeletal muscle protein synthesis remains USA, and Japan: Facts and numbers update 2016. J Cachexia
unknown, warranting further studies. Other signaling Sarcopenia Muscle. 2016;7(5):507-509.
pathways for beta-2 adrenergic agonists include tyrosine doi: 10.1002/jcsm.12167

Volume 8 Issue 1 (2025) 78 doi: 10.36922/itps.4699