The Non-Conventional Effects of Glucocorticoids in Cancer

Abstract

Synthetic corticosteroids are widely used for the treatment of a variety of diseases, including pre-malignant and malignant conditions. In striking contrast, recent evidence suggests that corticosteroids can bear tumor-promoting effects in solid tumors of epithelial origin. We have recently shown that epithelial tissues, including the mucosa of the oral cavity and the skin, are able to modulate the local concentration of active corticosteroids and to produce steroids de novo. This has important clinical and physiopathological implications, because tissue-specific regulation of glucocorticoids plays a key role in the overall effect of these molecules. In the present review of the current English literature, performed using MEDLINE/PubMed/Ovid databases, we collected published evidence to demonstrate that corticosteroids induce effects that are more complex and controversial than previously acknowledged. Published studies clearly demonstrate that this class of molecules influences pathophysiological processes that are strictly related to malignancy, providing the rationale for further investigation. J. Cell. Physiol. 231: 2368-2373, 2016. © 2016 Wiley Periodicals, Inc.

Glucocorticoids reduce chemotherapeutic effectiveness on OSCC cells via glucose‐dependent mechanisms

“…In the last few years, our focus has been directed on less known secondary effects of GCs, having collected evidence that GCs can influence a variety of functions such as cell migration, differentiation, apoptosis, and proliferation and may have tumor promoting effects, particularly in epithelial neoplasms (Azher et al, 2016).…”

“…Synthetic corticosteroids are routinely administered during the treatment of several diseases, including premalignant and malignant conditions, particularly to alleviate side effects of chemotherapy. Recent evidence suggests that corticosteroids may have tumor‐promoting effects, particularly in epithelial neoplasms (Azher et al, ; Herr & Pfitzenmaier, ). In view of the recent discovery of the CAG system, the role of glucocorticoids in the pathobiology of cancer requires further investigation.…”

Glucocorticoids promote a glioma stem cell‐like phenotype and resistance to chemotherapy in human glioblastoma primary cells: Biological and prognostic significance

“…In malignant brain tumors, GCs are a first line of care to decrease tumor‐associated brain inflammation and edema . However, the specific effect of GCs on cancer cells from solid tumors is largely disregarded in the clinic and remains only a topic of debate in experimental studies . Psychosocial stress, which increases endogenous GC levels, appears to influence the appearance of malignant brain tumors and correlates with poor prognosis in cancer patients .…”

“…10 However, the specific effect of GCs on cancer cells from solid tumors is largely disregarded in the clinic and remains only a topic of debate in experimental studies. 11 Psychosocial stress, which increases endogenous GC levels, appears to influence the appearance of malignant brain tumors and correlates with poor prognosis in cancer patients. 12 Moreover, previous studies indicate that GCs can have a profound impact on the gene expression profile of astrocytes and regulate the expression of astrocyte-derived growth factors that are implicated in the proliferation of neural precursor cells.…”

Role of tissue‐specific steroid metabolism in oral disease: Is there any clinical implication?

“…Glucocorticoids are routinely used in the management of blood malignancies but are also employed in the treatment of solid tumours (Haidar & Jeha, 2011). However, it has been suggested that systemic GCs can enhance energy metabolism, which may increase the ability of cancer cells to survive during radiation therapy and chemotherapy in vitro and in vivo (Azher et al, 2016;Seyfried, Shelton, & Mukherjee, 2010;Zhang et al, 2006). In fact, recent evidence shows that adjuvant dexamethasone administration compromises survival of patients with cancer (Pitter et al, 2016;Shields et al, 2015).…”