Title:Prevalence of Hepatocellular Carcinoma in Men and the Contribution of
Androgen and its Receptor in Pathogenesis and Therapy
Volume: 16
Author(s): Nabil Mohie Abdel-Hamid*Rawaa Muayad Al-Quzweny
Affiliation:
- Department of Biochemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt
Keywords:
Liver cancer, incidence, sex hormoness, androgen receptors, anti-androgen therapy, oestrogen.
Abstract:
Background: Hepatocellular carcinoma (HCC) is a solid cancer with high predominance
in males. Liver tissue of both genders has saturable specific oestrogen receptors. Androgen and its
receptor (AR) have been suggested to contribute to the predominance in men. Anti-oestrogens, like
tamoxifen may reduce the expression of oestrogen receptors, sustaining cellular in HCC. In vitro
and human, studies confirmed that both testosterone and dihydrotestosterone (DHT) enhanced the
growth and proliferation of hepatic normal and tumour cells. Although the activity of AR is escalated
by the chemical induction of hepatocarcinogenesis; clinical trials with AR-targeted agents alone
failed to generate survival benefits.
Purpose: This review will outline the possible pathophysiological mechanisms by which both androgen
and AR contribute to hepatocarcinogenesis and to which extent this pathway can be responsible
for the male prevalence and if they could be pharmacological targets in HCC management.
Conclusion: Influencing factors that seem to be responsible for male prevalence include testosterone,
dihydrotestosterone and androgen receptors, as well as, proteomic deficiency of DNA packaging,
nuclear proteins and homeostasis-related functional proteins. Understanding the reasons for
males, rather than females the HCC prevalence may help in suggesting new approaches by improving
the anti-AR therapies through co-targeting of AR and protein kinase B (Akt)/mammalian target
of rapamycin (mTOR) pathway.