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INNOSC Theranostics and
Pharmacological Sciences Anabolic agents in cancer cachexia

such as chromatin remodeling, cell cycle proliferation, of anabolic agents on cancer cachexia, Wright et al.
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and cell migration. In addition, the exclusion of nuclear reported that the administration of 100 mg of testosterone
steroid receptors and relegation to the cytoplasm may to cervical and head and neck cancer patients undergoing
be controlled by the interaction of these receptors and chemotherapy and chemoradiation resulted in a 3.2%
signaling and/or scaffold proteins. Androgens can activate increase in muscle mass in the testosterone group and
or repress histone activity through extranuclear and a 3.3% decline in the placebo group after 7 weeks of
nuclear mechanisms, thereby influencing protein signaling administration. There was no improvement in muscle
and exerting epigenetic effects. Androgens exert similar strength, physical performance, and survival, but there was
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effects in androgen receptor-positive tissues (prostate, an improvement in the quality of life. Limitations of this
breast, and skeletal muscle); these effects are generally study include the low dose of testosterone administered in
anabolic and/or proliferative responses. a life-threatening situation and the relatively short duration
of administration. Given the high risk of mortality in these
Another factor that affects the anabolic response
to androgens is the tumor microenvironment. For patients, this should encourage physicians and scientists to
example, tumor necrosis factor-alpha in the tumor adopt more aggressive approaches. The likelihood of liver
microenvironment is a negative regulator of protein problems is low with injectable testosterone or anabolic
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metabolism that promotes degradation and reduces steroids. In addition, the use of anabolic steroids (e.g.,
nandrolone decanoate) in high doses would be safer than
protein synthesis in muscles, suggesting competing high doses of testosterone due to the relative androgenicity
influences on the anabolic response to androgens.
between the two agents. The higher dose of testosterone
Isomers with the same chemical formula but different (600 mg/week) used in normal non-cancer patients by
atomic arrangements can affect receptor binding due Bhasin et al. resulted in a 6.1 kg increase in lean body mass
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to altered specificity. For example, glucose binds to its in healthy individuals. Moreover, the typical testosterone
receptor with much more binding affinity than fructose. cycle for a powerlifter involves 1 – 2 g/week, along with
Despite having the same chemical formula (C H O ), the 50 – 100 mg/day of Dianabol or Anadrol for 8 – 16 weeks.
6
12
6
fructose isomer has a lower binding affinity toward glucose These strength athletes live healthily and do not experience
receptors. immediate mortality after completing the cycle. 21
5. Repurposing of anabolic agents The anabolic response would be greater in a cancer
patient depleted of skeletal muscle compared to healthy
If the high mortality rates are not compelling enough, controls, due to a potential ceiling effect. Based on my
the lengthy time required to bring a new drug to market, understanding of floor and ceiling effects, anabolic
the immense cost of this process, and the countless lives agents should be used at all stages of cancer. Early use
lost during this period should be truly eye-opening. The could prevent a significant decline in muscle mass, and
entire process from drug discovery to full Food and Drug theoretically, the more negative the nitrogen balance, the
Administration (FDA) approval, inclusive of pre-clinical greater the corrective effect anabolic agents could have.
and clinical trials, takes approximately 10 – 15 years. At Notably, high-energy (kcals) and protein/amino-acid
a moderate mortality rate of 500,000/year, a 10-year FDA intake, either enterally or parenterally, should accompany
approval process would result in 5 million deaths in the high-dose testosterone or anabolic steroid administration
US. While repurposing anabolic agents may not save all in such a situation.
lives, bodybuilders allegedly taking these agents may gain
5 – 10 kg of muscle with resistance training in a short 6. Androgen sensitivity or androgen
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period. Bhasin et al. reported that healthy men receiving receptor presence in different tumor types
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600 mg/week of testosterone enanthate, combined with
resistance training, gained 6.1 kg of fat-free mass in 10 weeks. The presence of androgen receptors in tumors suggests
This accrual of skeletal muscle tissue in cancer patients that these tumors will grow when stimulated by androgens.
would allow time for other oncology practices, such as Therefore, for certain cancers, androgen receptor
chemotherapy, radiotherapy, surgery, and immunotherapy, stimulation using testosterone, anabolic steroids, and
to take effect and eliminate tumor-derived cancer. Cancer other androgens is not an option. One alternative is to
patients who die from cachexia are often believed to treat androgen-sensitive tumors with anabolic agents that
succumb to respiratory muscle atrophy and failure. do not stimulate the androgen receptor.
Considering the time, cost, and lives lost, it is imperative According to Viehweger et al. androgen receptor-
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to repurpose anabolic agents, such as testosterone and positivity, measured through immunohistochemistry, is
steroids. In the first clinical trial investigating the effects similar in testicular and ovarian stromal tumors as it is in

Volume 8 Issue 1 (2025) 77 doi: 10.36922/itps.4699