YK-11 and Cancer: Is There A Link?
Selective Androgen Receptor Modulators (SARMs) are a class of drugs that influence the androgen receptors. Androgen receptors are receptors in the nucleus that activate when an androgen hormone (such as testosterone or dihydrotestosterone), and signal to increase muscle mass and bone density. The SARMs are either agonists (activate the receptor) or antagonists (prevent hormone binding), and selectively target these receptors in different tissues, providing the benefits of androgen therapy (such as anabolic steroids) without the associated side effects (such as gynecomastia) [1].
SARMs have good oral bioavailability (function well when taken by mouth as a tablet) and transdermal bioavailability (can be formulated as a cream and diffuse through the skin), and thus present as an alternative to traditional androgen therapies [1].
Consequently, SARMs have been studied for therapeutic applications in a variety of conditions. These include:
- osteoporosis,
- Alzheimer's disease and other neurodegenerative diseases,
- urinary incontinence, benign prostatic hyperplasia, and other diseases of the prostate,
- muscular dystrophies,
- hypogonadism,
- a potential male contraception modality [1, 2].
SARMs in Cancer Therapy
SARMs have been investigated in cancer therapy, as the androgen receptors are relevant in some cancers, including prostate and breast cancers.
In prostate cancer, castration to reduce testosterone levels is a common treatment modality. An alternative to this treatment, or the follow-up treatment if the cancer is castration-resistant is to employ antiandrogenic SARMs [3]. In clinical trials, SARMs have been found to repress MYC oncoprotein expression and inhibit the growth of castration-sensitive and castration-resistant prostate cancer in vitro and in vivo [4].
In breast cancer, SARMs have been investigated for their anabolic effect without the adverse effects of anabolic steroids [2]. Androgen receptors are expressed in breast tumuors, and evidence suggests that they may be involved in estrogen receptor-mediated signalling, even in cancers that don't express estrogen receptors. There are several clinical trials investigating the use of SARMs in breast cancer, most of which show promise in Phase II [2].
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However, it is important to note that despite SARMs showing promise in cancer treatment, more research is needed to fully understand their role in modern cancer medicine, as well as establish a comprehensive safety profile.
What is YK-11?
YK-11 is a steroidal SARM, which is a partial agonist of the androgen receptor [5]. The molecule gained popularity among fitness enthusiasts and athletes as a performance enhancing drug due to its action in stimulating muscle growth, while also inhibiting myostatin, which is a protein that inhibits muscle differentiation and growth [6]. Additionally, the effect on bone mineralisation is also beneficial in athletes [7].
Should YK-11 be used in medicine?
Chemically, YK-11 shows interesting properties, as it has high brain permeability, meaning that it can pass through the blood-brain barrier, which is very difficult for cells and molecules to cross [6]. Interesting mechanisms of action of YK-11 have been described, including:
- neurochemical functions with beneficial effects on memory [6],
- activation of the Akt-signalling pathway, which is a key regulator of bone grotwh,
- myostatin inhibition.
While there are apparent benefits with YK-11 use, it is important to note that there are potential severe risks. Due to its effects in the brain, studies have shown that YK-11 can significantly alter hippocampal neurochemistry, leading to impairments in memory consolidation [6].
Additionally, YK-11 was also shown to promote oxidative stress, which refers to a molecular imbalance in the cell which can lead to DNA damage and cancer [8]. However, as YK-11 is a relatively novel molecule, further research is required to build a comprehensive safety profile.
YK-11 in cancer treatment: What is the evidence?
YK-11 is not used in cancer treatment currently. The data on the potential roles of YK-11 in cancer treatment are scarce, however, androgen receptor agonists are not routinely used. In prostate cancer, it is anti-androgenic medication (receptor antagonists) that are used.
However, in a recent study, the mechanism of nuclear signalling induced by YK-11 binding was elucidated, and the study concluded that the molecule alters expression of genes some of which are implicated in survival of the breast cancer cells [9]. However, further research needs to be completed to understand the role of YK-11 in cancer treatment.