The effect of placentation type, litter size, lactation and gestation length on cancer risk in mammals DOI Open Access
Antoine M. Dujon, Orsolya Vincze, Jean‐François Lemaître

et al.

Proceedings of the Royal Society B Biological Sciences, Journal Year: 2023, Volume and Issue: 290(2001)

Published: June 26, 2023

Reproduction is a central activity for all living organisms but also associated with diversity of costs that are detrimental survival. Until recently, the cost cancer as selective force has been poorly considered. Considering 191 mammal species, we found mortality was more likely to be detected in species having large, rather than low, litter sizes and long lactation lengths regardless placentation types. However, increasing size gestation length not per se an enhanced risk. Contrary basic theoretical expectations, highest were those most invasive (i.e. haemochorial) placentation, moderately endotheliochorial) one. Overall, these results suggest (i) high reproductive efforts favour oncogenic processes' dynamics, presumably because trade-offs between allocation reproduction effort anti-cancer defences, (ii) defence mechanisms animals often adjusted align lifespan, (iii) malignant cells co-opt existing molecular physiological pathways have selected potent barriers against lethal cancers. This work suggests logic Peto's paradox seems applicable other traits promote tumorigenesis.

Language: Английский

Sex and gender: modifiers of health, disease, and medicine DOI Creative Commons
Franck Mauvais‐Jarvis, C. Noel Bairey Merz, Peter J. Barnes

et al.

The Lancet, Journal Year: 2020, Volume and Issue: 396(10250), P. 565 - 582

Published: Aug. 1, 2020

Clinicians can encounter sex and gender disparities in diagnostic therapeutic responses. These are noted epidemiology, pathophysiology, clinical manifestations, disease progression, response to treatment. This Review discusses the fundamental influences of as modifiers major causes death morbidity. We articulate how genetic, epigenetic, hormonal biological influence physiology disease, social constructs affect behaviour community, clinicians, patients health-care system interact with pathobiology. aim guide clinicians researchers consider their approach diagnosis, prevention, treatment diseases a necessary step towards precision medicine, which will benefit men's women's health.

Language: Английский

Citations

1472
Sex disparities matter in cancer development and therapy DOI
Sue Haupt, Franco Caramia, Sabra L. Klein

et al.

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(6), P. 393 - 407

Published: April 20, 2021

Language: Английский

Citations

221
Sexual Dimorphism in Colon Cancer DOI Creative Commons

Maria Abancens,

Viviana Bustos,

Harry Harvey

et al.

Frontiers in Oncology, Journal Year: 2020, Volume and Issue: 10

Published: Dec. 9, 2020

A higher incidence of colorectal cancer (CRC) is found in males compared to females. Young women (18-44 years) with CRC have a better survival outcome men the same age or older (over 50 years), indicating global sexual dimorphism rates and survival. This suggests protective role for sex steroid hormone estrogen development. Key proliferative pathways tumorigenesis exhibit dimorphism, which confer females through regulated genes cell signaling. Estrogen regulates activity class Kv channels (KCNQ1:KCNE3), control fundamental ion transport functions colon epithelial mesenchymal transition bi-directional interactions Wnt/β-catenin signalling pathway. also modulates responses hypoxia

Language: Английский

Citations

143
Sex-Specific Differences in Glioblastoma DOI Creative Commons
Anna Carrano, Juan José Juárez‐Vignon Whaley, Diego Incontri‐Abraham

et al.

Cells, Journal Year: 2021, Volume and Issue: 10(7), P. 1783 - 1783

Published: July 14, 2021

Sex differences have been well identified in many brain tumors. Even though glioblastoma (GBM) is the most common primary malignant tumor adults and has worst outcome, well-established between men women are limited to incidence outcome. Little known about sex GBM at disease phenotype genetical/molecular level. This review focuses on a deep understanding of pathophysiology GBM, including hormones, metabolic pathways, immune system, molecular changes, along with how these dimorphisms affect The information analyzed this shows greater worse outcome male patients compared female patients. We highlight protective role estrogen upregulation androgen receptors testosterone having detrimental effects GBM. Moreover, hormones system work synergy directly microenvironment. Genetic also recently identified. Specific genes either upregulated or downregulated depending sex, could potentially dictate differences. It appears that sexual dimorphism affects patient requires an individualized approach management considering patient, especially relation

Language: Английский

Citations

107
Androgen receptor blockade promotes response to BRAF/MEK-targeted therapy DOI
Christopher P. Vellano, Michael G. White, Miles C. Andrews

et al.

Nature, Journal Year: 2022, Volume and Issue: 606(7915), P. 797 - 803

Published: June 15, 2022

Language: Английский

Citations

95
The spectrum of sex differences in cancer DOI Creative Commons
Joshua B. Rubin

Trends in cancer, Journal Year: 2022, Volume and Issue: 8(4), P. 303 - 315

Published: Feb. 18, 2022

HighlightsSex differences in cancer incidence and survival are the norm evident across types, around globe, all genetic ancestries, age groups.Increasingly, sex cancer-relevant cellular systems biology being described.Sex mutational burden, DNA repair, epigenetics, metabolism, tumor suppressor activity, cell cycle regulation, immunity reported.AbstractSex have been evolutionarily selected to optimize reproductive success species with little (sperm) big (ova) gamete producers. They from time of fertilization accrue throughout development through genetic, epigenetic, circulating hormone-dependent mechanisms. Among other effects, they significantly impact on chromatin organization, immunity, longevity, risk survival. Sex should be expected accounted for basic, translational, clinical oncology research.

Language: Английский

Citations

80
The Role of Epigenetic Modifications in Human Cancers and the Use of Natural Compounds as Epidrugs: Mechanistic Pathways and Pharmacodynamic Actions DOI Creative Commons
Abdelhakim Bouyahya, Hamza Mechchate, Loubna Oumeslakht

et al.

Biomolecules, Journal Year: 2022, Volume and Issue: 12(3), P. 367 - 367

Published: Feb. 25, 2022

Cancer is a complex disease resulting from the genetic and epigenetic disruption of normal cells. The mechanistic understanding pathways involved in tumor transformation has implicated priori predominance perturbations posteriori instability. In this work, we aimed to explain involvement cancer process, as well abilities natural bioactive compounds isolated medicinal plants (flavonoids, phenolic acids, stilbenes, ketones) specifically target epigenome molecular events leading transformation, angiogenesis, dissemination are often complex, stochastic, take turns. On other hand, decisive advances genomics, epigenomics, transcriptomics, proteomics have allowed, recent years, for decryption cancerization process. This could possibility targeting or that mechanism cancerization. With plasticity flexibility modifications, some studies started pharmacological screening substances against different (DNA methylation, histone acetylation, chromatin remodeling) restore cellular memory lost during transformation. These can inhibit DNMTs, modify remodeling, adjust modifications favor pre-established cell identity by differentiation program. Epidrugs molecules program therefore cancerous diseases. Natural products such flavonoids acids shown their ability exhibit several actions on modifiers, inhibition DNMT, HMT, HAT. mechanisms these specific pleiotropic sometimes be use anticancer epidrugs currently remarkable avenue fight human cancers.

Language: Английский

Citations

79
Histone demethylase KDM5D upregulation drives sex differences in colon cancer DOI
Jiexi Li,

Zhengdao Lan,

Wenting Liao

et al.

Nature, Journal Year: 2023, Volume and Issue: 619(7970), P. 632 - 639

Published: June 21, 2023

Language: Английский

Citations

76
Sex-Biased T-cell Exhaustion Drives Differential Immune Responses in Glioblastoma DOI Creative Commons
Juyeun Lee, Michael Nicosia, Ellen S. Hong

et al.

Cancer Discovery, Journal Year: 2023, Volume and Issue: 13(9), P. 2090 - 2105

Published: June 28, 2023

Abstract Sex differences in glioblastoma (GBM) incidence and outcome are well recognized, emerging evidence suggests that these extend to genetic/epigenetic cellular differences, including immune responses. However, the mechanisms driving immunologic sex not fully understood. Here, we demonstrate T cells play a critical role GBM differences. Male mice exhibited accelerated tumor growth, with decreased frequency increased exhaustion of CD8+ tumor. Furthermore, higher progenitor exhausted was found males, improved responsiveness anti–PD-1 treatment. Moreover, T-cell observed male patients. Bone marrow chimera adoptive transfer models indicated cell–mediated control predominantly regulated cell-intrinsic manner, partially mediated by X chromosome inactivation escape gene Kdm6a. These findings sex-biased predetermined behavior is for inducing progression immunotherapy response. Significance: Immunotherapies patients have been unsuccessful due variety factors, highly immunosuppressive microenvironment GBM. This study demonstrates behaviors intrinsically regulated, further suggesting sex-specific approaches can be leveraged potentially improve therapeutic efficacy See related commentary Alspach, p. 1966. article featured Selected Articles from Issue, 1949

Language: Английский

Citations

56
Genome-Wide Sex and Gender Differences in Cancer DOI Creative Commons
Camila M. Lopes‐Ramos, John Quackenbush, Dawn L. DeMeo

et al.

Frontiers in Oncology, Journal Year: 2020, Volume and Issue: 10

Published: Nov. 23, 2020

Despite their known importance in clinical medicine, differences based on sex and gender are among the least studied factors affecting cancer susceptibility, progression, survival, therapeutic response. In particular, molecular mechanisms driving poorly understood so most approaches to precision medicine use mutational or other genomic data assign therapy without considering how of individual might influence efficacy. The mandate by National Institutes Health that research studies include as a biological variable has begun expand our understanding its importance. Sex may arise due combination environmental, genetic, epigenetic factors, well gene regulation, expression. Extensive occur genome-wide, ultimately biology outcomes. this review, we summarize current state knowledge about sex-specific genetic genome-wide influences cancer, describe response environmental exposures alterations alter trajectory disease, provide insights into integrative analyses interplay genomics cancer. will explore some emerging analytical approaches, such network methods, providing deeper drivers gender. Better these complex interactions improve prevention, treatment, outcomes for all individuals.

Language: Английский

Citations

119