Sexual dimorphism in molecular biology of cancer

Dorak, Mehmet (2023) Sexual dimorphism in molecular biology of cancer. In: Legato, Marianne J., (ed.) Principles of Gender-Specific Medicine: Sex and Gender-Specific Biology in the Postgenomic Era. 4th ed. London, U.K. : Academic Press. pp. 463-476. ISBN 9780323885348


Cancer is one of the complex disorders that show sexual dimorphism in its susceptibility, clinical course, response to treatment, and prognosis. Most cancers show a disadvantage for males. Although a few of the molecular mechanisms of higher susceptibility of males to cancer development have been documented, most remain elusive. This chapter will review the current status of this field and explore possible mechanisms which involve sex chromosomes, gene expression regulation, and epigenetics. Recent research showed that both X and Y chromosomes influence the sex bias in cancer; sex hormones have obvious effects but not necessarily always via their dedicated receptors, and there are sex hormone–binding membrane receptors besides the nuclear sex hormone receptors. Regulatory networks (transcription factors) may have sex-specific targeting patterns even when they do not have sexual dimorphism in expression levels. All of these have implications for sexual dimorphism in cancer that await elaboration. Intriguing questions identified for future research include the role of sex-specific gene expression that begins before implantation, the role of variations in sex hormone levels in mini puberty during infancy, and the mechanism of the reversal of sex-differential in susceptibility to cancer at adolescence for Hodgkin lymphoma. Ultimately though, the biggest challenge is the conversion of the preclinical data to clinical practice for tailored treatment for each sex. With ever-increasing awareness of sexual dimorphism in cancer and its implications for personalized medicine, we can be optimistic that soon we may see most of the gaps in knowledge filled and clinical utility fulfilled.

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