The prognostic and therapeutic role of hormones in colorectal cancer: a review

Nikolaou, Stella; Qiu, Shihui; Fiorentino, Francesca; Tekkis, Paris; Kontovounisios, Christos

doi:10.1007/s11033-018-4528-6

Cited by 20 publications

(14 citation statements)

References 74 publications

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“…In contrast, after diabetes induction through HFD, mice models lacking adiponectin (Apn −/− ) were more prone to CRC development through AOM treatment (Parida et al 2019) or chronic inflammation (Otani et al 2017). Consistent with previous results, AdipoRon, a synthetic adiponectin analogue diminished the proliferation in early CRC stages and prevented CRC related to T2D (Nikolaou et al 2019). Notably, AdipoRon also improved insulin resistance and glucose tolerance in obese, diabetic mouse models suggesting that its effects may be mediated by insulin, glucose or other factors.…”

Section: Unbalanced Leptin/adiponectin In T2d Impacts Crcsupporting

confidence: 88%

“…In vitro, leptin stimulates CRC cell proliferation through the modulation of PI3K/Akt/mTOR, GSK3B and MAPK pathways, Fig. 3 (Aparicio et al 2005, Ghasemi et al 2019; leptin exerts anti-apoptotic effects via PI3K/Akt, JAK2/ STAT3 and JNK pathways (Nikolaou et al 2019); leptin induces migration and invasion in CRC cells through the Src/Rac1/Cdc42, MAPK and PKCD pathways (Fig. 3) (Ghasemi et al 2019).…”

Section: Unbalanced Leptin/adiponectin In T2d Impacts Crcmentioning

confidence: 99%

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Metabolic and hormonal remodeling of colorectal cancer cell signaling by diabetes

Gutiérrez-Salmerón

Lucena

Chocarro-Calvo

et al. 2021

Endocrine-Related Cancer

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The existence of molecular links that facilitate colorectal cancer (CRC) development in the population with type 2 diabetes (T2D) is supported by substantial epidemiological evidence. This review summarizes how the systemic metabolic and hormonal imbalances from T2D alter CRC cell metabolism, signaling and gene expression as well as their reciprocal meshing, with an overview of CRC molecular subtypes and animal models to study the diabetes-CRC cancer links. Metabolic and growth factor checkpoints ensure a physiological cell proliferation rate compatible with limited nutrient supply. Hyperinsulinemia and hyperleptinemia in prediabetes and excess circulating glucose and lipids in T2D, overcome formidable barriers for tumor development. Increased nutrient availability favours metabolic reprogramming, alters signaling and generate mutations and epigenetic modifications, through increased reactive oxygen species and oncometabolites. The reciprocal control between metabolism and hormone signaling is lost in diabetes. Excess adipose tissue at the origin of T2D, unbalances adipokine (leptin / adiponectin) secretion ratios and function and disrupts the Insulin/IGF axes. Leptin/adiponectin imbalances in T2D are believed to promote proliferation and invasion of CRC cancer cells and contribute to inflammation, an important component of CRC tumorigenesis. Disruption of the Insulin/IGF axes in T2D targets systemic and CRC cell metabolic reprogramming, survival and proliferation. Future research to clarify the molecular diabetes-CRC links will help to prevent CRC and reduce its incidence in the diabetic population and must guide therapeutic decisions.

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Section: Unbalanced Leptin/adiponectin In T2d Impacts Crcsupporting

confidence: 88%

Section: Unbalanced Leptin/adiponectin In T2d Impacts Crcmentioning

confidence: 99%

Metabolic and hormonal remodeling of colorectal cancer cell signaling by diabetes

Gutiérrez-Salmerón

Lucena

Chocarro-Calvo

et al. 2021

Endocrine-Related Cancer

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“…With the majority of women in the post-menopausal stage at CRC diagnosis, the sexual dimorphism in more elderly CRC incidence rates may not entirely be due to sex hormones unless these have a protective effect during child-bearing years to delay the onset of CRC. There is still much debate how sex hormones, which are known to be carcinogenic in a wide number of tissues may exert protective effects in the colon ( 8 , 9 ). In spite of the great variability in CRC incidence rates from one region of the world to the next, sexual dimorphism in colon cancer incidence rates is consistently observed for countries in Europe, the Americas and Asia ( Figure 2 ).…”

Section: Introductionmentioning

confidence: 99%

Sexual Dimorphism in Colon Cancer

et al. 2020

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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 compared to men of the same age or compared to older women (over 50 years), indicating a global incidence of sexual dimorphism in CRC rates and survival. This suggests a protective role for the sex steroid hormone estrogen in CRC development. Key proliferative pathways in CRC tumorigenesis exhibit sexual dimorphism, which confer better survival in females through estrogen regulated genes and cell signaling. Estrogen regulates the activity of a class of Kv channels (KCNQ1:KCNE3), which control fundamental ion transport functions of the colon and epithelial mesenchymal transition through bi-directional interactions with the Wnt/β-catenin signalling pathway. Estrogen also modulates CRC proliferative responses in hypoxia via the novel membrane estrogen receptor GPER and HIF1A and VEGF signaling. Here we critically review recent clinical and molecular insights into sexual dimorphism of CRC biology modulated by the tumor microenvironment, estrogen, Wnt/β-catenin signalling, ion channels, and X-linked genes.

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“…However, the reasons leading to this effect remain unclear. One possible influencing factor with therapeutic potential is the hormone balance [6]. Furthermore, sex-dependent differences in the administration of adjuvant chemotherapy have been described [7].…”

Section: Introductionmentioning

confidence: 99%

Gender comparison of clinical, histopathological, therapeutic and outcome factors in 185,967 colon cancer patients

Schmuck

Gerken

Teegen

et al. 2020

Langenbecks Arch Surg

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Introduction Colorectal carcinomas represent the third most common cause of cancer-related deaths in Germany. Although the incidence is significantly higher in men compared with women and gender is a well-established crucial factor for outcome in other diseases, detailed gender comparisons for colon cancer are lacking. Methods This retrospective population-based cohort study included all patients diagnosed with colon cancer in Germany between 2000 and 2016 who were included in the common dataset of colorectal cancer patients from the quality conference of the German Cancer Society. We compared clinical, histopathological, and therapeutic characteristics as well as overall and recurrence-free survival. Results A total of 185,967 patients were included in the study, of which 85,685 were female (46.1%) and 100,282 were male (53.9%). The proportion of women diagnosed with colon cancer decreased from 2000 to 2016 (f: 26.6 to 40.1%; m: 24.9 to 41.9%; p < 0.001), and the proportion of very old patients was especially high in women (f: 27.3%; m: 15.6%; p < 0.001). The localization in women was more right-sided (f: 45.0%, m: 36.7%; p < 0.001), and women had a higher tumor grading and a higher UICC stage (especially stage III nodal-positive) at diagnosis of primary colon cancer (UICC III: f: 22.7%, m: 21.0%; p < 0.001). We could detect a significantly better overall (hazard ratio: 0.853, lower 95%: 0.841, upper 95%: 0.864; p < 0.001) and recurrence-free survival (hazard ratio: 0.857, lower 95%: 0.845, upper 95%: 0.868; p < 0.001) in women compared with men, even though women received chemotherapy less frequently compared with men (f: 26.1%, m: 28.1%; p < 0.001). Highlights • Women are older than men at diagnosis of primary colon cancer • The localization in women tends to be right-sided, and women tend to have a higher tumor grading and a higher UICC stage (especially stage III nodal-positive) • Women show a better overall and recurrence-free survival compared with men • Women receive chemotherapy less frequently than men do Electronic supplementary material The online version of this article (

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The prognostic and therapeutic role of hormones in colorectal cancer: a review

Cited by 20 publications

References 74 publications

Metabolic and hormonal remodeling of colorectal cancer cell signaling by diabetes

Metabolic and hormonal remodeling of colorectal cancer cell signaling by diabetes

Sexual Dimorphism in Colon Cancer

Gender comparison of clinical, histopathological, therapeutic and outcome factors in 185,967 colon cancer patients

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