Cell cycle arrest by glucocorticoids may protect normal tissue and solid tumors from cancer therapy.
Glucocorticoids have been widely used as cotreatment for patients with cancer due to potent pro-apoptotic properties in lymphoid cells, reduction of nausea and diminishing acute toxicity on normal tissue. There are now data from preclinical and, to some extent, clinical studies, demonstrating that these medicaments are highly suspicious to induce therapy resistance in the majority of malignant solid tumors-irrespective of tumor origin and the nature of specific anticancer drugs or irradiation used for treatment. Despite these huge amounts of data, the underlying mechanisms of cell type-specific signaling by these steroid hormones are just beginning to be described. This review summarizes our present understanding of a relationship between glucocorticoid-induced reversible cell cycle arrest and therapy resistance in solid tumors. We give a summary of our current knowledge of decreased proliferation rates in response to glucocorticoid pre and combination treatment which are suspicious to be involved not only in protection of normal tissues, but also in protection of solid tumors from cytotoxic effects of anticancer agents. The inhibition of cell cycle progression by pretreatment with GCs may be crucially involved in switching the balance of several interacting pathways to survival upon treatment with GCs.
Mattern
Jürgen
J
Molecular OncoSurgery, Department of Surgery, University and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Büchler
Markus W
MW
Herr
Ingrid
I
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy*; D015398:Signal Transduction; D013256:Steroids / Q000378:metabolism
D000970:Antineoplastic Agents; D005938:Glucocorticoids; D013256:Steroids; D003907:Dexamethasone