Testosterone and Androgen Receptor in Cancers with Significant Sex Dimorphism in Incidence Rates and Survival

Area of Science:

• Oncology
• Endocrinology
• Cancer Biology

Background:

• Significant sex dimorphism exists in cancer incidence and survival rates.
• Understanding sex as a biological factor is crucial for developing precise cancer prevention and treatment strategies.

Purpose of the Study:

• To review epidemiological and molecular data on sex differences in major cancers.
• To investigate the role of androgens and androgen receptor (AR) activity in tumorigenesis, progression, and survival.
• To explore potential therapeutic strategies targeting the androgen pathway.

Main Methods:

• Review of epidemiological data on sex differences in esophagus, bladder, head and neck, lung, liver, kidney, stomach, and skin melanoma.
• Analysis of molecular data concerning androgen and AR activity in these cancers.
• Discussion of potential molecular mechanisms and clinical implications.

Main Results:

• Testosterone (T) associated with increased liver cancer and melanoma risk, and reduced esophageal cancer risk.
• AR expression linked to poorer survival in esophageal squamous cell carcinoma (ESCC); inconsistent role in head and neck squamous cell carcinoma (HNSCC) and melanoma.
• AR likely promotes tumor growth in esophagus, bladder, head and neck, and stomach cancers, correlating with poor survival.

Conclusions:

• AR may be a therapeutic target for esophagus, bladder, head and neck, and stomach cancers.
• Research on androgens and AR in these cancers is limited, necessitating further investigation.
• Deciphering the role of T and AR is vital for understanding sex dimorphism and developing novel T/AR-based treatments.