Chapter 6 Mechanisms Regulating the Susceptibility of Hematopoietic Malignancies to Glucocorticoid‐Induced Apoptosis

Sionov, Ronit Vogt; Spokoini, Rachel; Kfir‐Erenfeld, Shlomit; Cohen, Orly; Yefenof, Eitan

doi:10.1016/s0065-230x(08)00406-5

Cited by 73 publications

(88 citation statements)

References 711 publications

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“…39,40 It is also well established the importance of GCs in perinatal lung development. 41,42 However, these compounds have therapeutic effects on some childhood and hematological malignancies [20][21][22] but not in lung cancer or most solid tumors. 42,43 There is a physical interaction between components of the SWI/ SNF complex and the RA and GC receptors and there is evidence of nucleosome-disrupting activity of the complex to allow transcription mediated by RA and GC receptors.…”

Section: Resultsmentioning

confidence: 99%

“…Such is the case for neuroblastomas, with NMYC amplification, and Burkitt lymphoma, which is associated with translocations involving MYC. [20][21][22] Furthermore, the BET bromodomain inhibitor JQ1, which triggers the downregulation of MYC, has antiproliferative effects in those multiple myeloma cells and neuroblastomas that carry MYC translocations and MYCN amplification, respectively. 47 Taking into account that activated oncogenes are an Achilles heel for most cancer cells, a treatment that triggers MYC downregulation may be expected to be more efficient in cancers with genetically activated MYC.…”

Section: Resultsmentioning

confidence: 99%

“…GC are part of the curative treatment of acute lymphoblastic leukemia while RA is the therapeutic agent for some neuroblastomas and acute promyelocytic leukemia, which both carry the promyelocytic leukemia-RA receptor alpha gene fusion. [20][21][22] GC are also used as a comedication to reduce side effects in cancer treatment. 23 However, most solid tumors, including lung cancers, are refractory to GC-and RA-based therapies.…”

Section: Introductionmentioning

confidence: 99%

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Sensitization of retinoids and corticoids to epigenetic drugs in MYC-activated lung cancers by antitumor reprogramming

et al. 2016

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sensitization of retinoids and corticoids to epigenetic drugs in MYC-activated lung cancers by antitumor reprogramming

et al. 2016

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“…Glucocorticoids (Gcs) are widely used for the treatment of lymphoid malignancy (Pirotte et al 1997, Sionov et al 2008 because of their dramatic effects on cell cycle progression and apoptosis. They are also used as a co-medication in the therapy of solid tumours, either because of their effectiveness in treating the malignancy, or for decreasing oedema, pain, electrolyte imbalance, nausea and emesis or to reduce cytotoxic reactions caused by other treatment regimens (Rutz 2002, Rutz & Herr 2004.…”

Section: Glucocorticoid Treatment Of Cancermentioning

confidence: 99%

Glucocorticoid receptor-mediated apoptosis: mechanisms of resistance in cancer cells

Schlossmacher

Stevens²,

White

2011

Journal of Endocrinology

137

110

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Glucocorticoids (Gcs) are commonly used to treat patients suffering from a wide range of cancers. Their main therapeutic role is based on Gc receptor (GR)-mediated mechanisms that trigger cell death but this varies depending on the cancer type. This review aims to provide an overview of the mechanisms of Gc-induced cell death and more importantly the changes in GR that lead to resistance to Gc treatment in cancer. The three main cancer types, which are susceptible to Gc resistance and therefore loss of Gc-induced apoptotic effects, are acute lymphoblastic leukaemia, osteosarcoma and small-cell lung carcinoma. A common theme is the loss of GR function and/or a downregulation of GR expression which leads to failure of the cell death-inducing effects of Gcs. Loss of GR function is attributed to mutations in the GR gene, and in some cases a dominant-negative effect on any functional GR still present. The downregulation of GR expression can be due to decreased GR promoter activation, increased GR promoter methylation or increased expression of alternative splice isoforms of GR that have decreased transcriptional activity. Understanding the mechanisms behind Gc-triggered apoptosis and the resistance to it in these cancer types will help in further refining treatment regimens for patients and will decrease the chance of relapse caused by Gc-resistant cancer phenotypes.

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“…GCs have been used to treat diseases caused by an overactive immune system, such as allergies, asthma, and autoimmune diseases as well as a broad spectrum of hematologic malignancies, including leukemia, lymphoma, and myeloma due to their ability to induce apoptosis [16][17][18]. Recent studies found the inhibitory effect of GCs to COX-2 could suppress solid tumor growth, regress tumor mass, and prevent metastasis by blocking angiogenesis [19,20].…”

Section: Cyclooxygenase-2 and Glucocorticoids In Tumorigenesismentioning

confidence: 99%

11β-hydroxysteroid dehydrogenase type II: a Potential target for prevention of colonic tumorigenesis

Wang¹,

Harris²,

Zhang³

2016

Integr Cancer Sci Therap

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Cancer is the second most common cause of death in the world, and primary prevention remains the best approach to reducing overall morbidity and mortality. There is a molecular link between cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) production and colonic tumorigenesis. Selective COX-2 inhibitors as well as non-steroidal anti-inflammatory drugs (NSAIDs) reduce the number and sizes of colonic adenomas; however, increased cardiovascular risks of selective COX-2 inhibitors and increased gastrointestinal side-effects of NSAIDs limit their use. Glucocorticoids induce cancer cell apoptosis and are endogenous, potent COX-2 inhibitors. In tissues, glucocorticoid actions are down-regulated by type 2 11ß-hydroxysteroid dehydrogenase (11ßHSD2), and inhibition of 11ßHSD2 activity will elevate intracellular active glucocorticoids to levels that effectively suppress COX-2 expression. Both COX-2 and 11ßHSD2 increase in Apc+/min mouse intestinal adenomas and human colonic adenomas, and either pharmacologic or genetic 11βHSD2 inhibition leads to decreases in COX-2-mediated PGE2 production in tumors and prevents adenoma formation, tumor growth, and metastasis. 11ßHSD2 inhibition may represent a novel approach for CRC chemoprevention by increasing tumor cell intracellular glucocorticoid activity, which in turn inhibits tumor growth by suppressing the COX-2-derived PGE2 pathway, as well as other pathways, without potential side-effects relating to chronic application of COX-2 inhibitors, NSAIDs and glucocorticoids.

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Chapter 6 Mechanisms Regulating the Susceptibility of Hematopoietic Malignancies to Glucocorticoid‐Induced Apoptosis

Cited by 73 publications

References 711 publications

Sensitization of retinoids and corticoids to epigenetic drugs in MYC-activated lung cancers by antitumor reprogramming

Sensitization of retinoids and corticoids to epigenetic drugs in MYC-activated lung cancers by antitumor reprogramming

Glucocorticoid receptor-mediated apoptosis: mechanisms of resistance in cancer cells

11β-hydroxysteroid dehydrogenase type II: a Potential target for prevention of colonic tumorigenesis

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