The androgen receptor (AR) pathway is critical for prostate cancer carcinogenesis and development, however, after 18-24 months of AR blocking therapy, patients invariably progress to castration-resistant prostate cancer (CRPC), which remains an urgent problem to be solved.
These findings provide critical information on the roles of GR and AR steroid receptors in SDC tumorigenesis and may lead to the development of a biomarker-based strategy to guide targeted steroid receptor therapy trials in patients with these tumors.
Therefore, the regulation of AR protein stability and its degradation is another interesting path that could enhance our knowledge of carcinogenesis and tumor evolution possibly leading to novel therapeutic targets.
Androgen receptor (AR) stimulators, such as androgen and Tip60, play a pivotal role in prostatic carcinogenesis as androgen receptor signaling is critical for the growth and transformation of the prostate gland.
ETS status influences the transcriptional repertoire of the AR, and ETS- PCa tumors appear to rely on distinctly different AR-dependent transcriptional programs to drive and sustain tumorigenesis.
In prostate carcinogenesis, androgens are known to control the expression of the transient receptor potential melastatin 8 (TRPM8) protein via activation of androgen receptor (AR).
Concerning prostate cancer, the androgen receptor (AR) is majorly involved in tumorigenesis, while CDK5 can phosphorylate AR and promotes the proliferation of prostate cancer cells.
Androgen receptor (AR) and its variants (AR-Vs) promote tumorigenesis and metastasis in many hormone-related cancers, such as breast, prostate and hepatocellular cancers.
However, despite the diversity of tumor-initiating cells, most prostate cancer cells express the androgen receptor (AR) and depend on androgens for their growth and expansion, implicating an essential role of androgen signaling in prostate tumorigenesis.
This review summarizes and discusses the available data indicating the involvement of androgens as well as androgen receptor and related signals in ovarian carcinogenesis and cancer growth.
Class-1 activating mutations originate in early prostate cancer without alterations in ETS or SPOP, selectively recur within the wing-2 region of the DNA-binding forkhead domain, enable enhanced chromatin mobility and binding frequency, and strongly transactivate a luminal androgen-receptor program of prostate oncogenesis.
Overproduction of GABA, an oncometabolite, can directly regulate nuclear androgen receptor signaling to drive tumorigenesis, thereby providing a link between aberrant metabolism and protumorigenic signaling in advanced prostate cancer.
Interestingly, three major subgroups of genomic subcomplexes were identified, where selective gain of function for AR genomic action in tumorigenesis was found, dictated by FOXA1 and HOXB13.
The HER2E subtype has a distinctive transcriptional landscape independent of HER2A that reflects androgen receptor signaling as replacement for estrogen receptor (ER)-driven tumorigenesis.
In the prostate, androgen receptor (AR) is a master regulator essential for development and tumorigenesis, but its specific functions in prostate stem/progenitor cells have not been elucidated.
However, the role of AR in breast cancer development and progression is mired in controversy with evidence suggesting it can either inhibit or promote breast tumorigenesis.
The notion that androgens and androgen receptor (AR) signaling are the hallmarks of prostate cancer oncogenesis and disease progression is generally well accepted.
Preclinical models have demonstrated that androgen receptor modulation can influence bladder carcinogenesis with an inverse association observed between serum androgen levels and bladder cancer (BC) incidence.