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

Abstract

Colorectal cancer (CRC) is one of the commonest cancers in Western society with a poor prognosis in patients with advanced disease. Targeted therapy is of increasing interest and already, targeted hormone treatment for breast and prostate cancer has improved survival. The aim of this literature review is to summarise the role of hormones in CRC prognosis and treatment. A literature review of all human and animal in vivo and in vitro studies in the last 20 years, which assessed the role of hormones in CRC treatment or prognosis, was carried out. The hormones described in this review have been subdivided according to their secretion origin. Most of the studies are based on in vitro or animal models. The main findings point to adipokines, insulin and the insulin growth factor axis as key players in the link between obesity, type 2 diabetes mellitus and a subset of CRC. Gut-derived hormones, especially uroguanylin and guanylin are being increasingly investigated as therapeutic targets, with promising results. Using hormones as prognostic and therapeutic markers in CRC is still in the preliminary stages for only a fraction of the hormones affecting the GIT. In light of the increasing interest in tailoring treatment strategies, hormones are an important area of focus in the future of CRC management.

Metabolic and hormonal remodeling of colorectal cancer cell signaling by diabetes

“…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.…”

“…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).…”

Sexual Dimorphism in Colon Cancer

“…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 ).…”

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

“…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].…”