Novel Endocrine Therapies in Breast Cancer

Klijn, J.G.M.; Setyono-Han, Buddy; Bontenbal, M.; Seynaeve, C.; Foekens, John A.

doi:10.3109/02841869609083965

Cited by 6 publications

(2 citation statements)

References 59 publications

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“…They produce a modest and shortlasting response in a subgroup of such patients, and, as a rule, they are the more efficient as the first-line hormone therapy has been efficient [103]. Progesterone-derived molecules (megestrol, medroxyprogesterone) are used in second line, i.e.…”

Section: Therapy Addressing Targets Other Than Er Progestagensmentioning

confidence: 99%

Proliferation of Breast Cancer Cells: Regulation, Mediators, Targets for Therapy

Mešter¹,

Redeuilh²

2008

ACAMC

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A majority of breast cancers (BC) display characteristics of epithelial cells and express estrogen receptors and/or HER-2 (a member of the epidermal growth factor receptor family). About one-fifth of BC is constituted of basal cells for which there is no specific category of proliferation regulators. Insulin-like growth factor (IGF) signaling is involved in most BC cells, irrespective of cell type. All inducers of cell proliferation employ transcriptional as well as non-transcriptional mechanisms to activate the cascade of cyclin-dependent kinases, which causes irreversible progression to the G1/S phase transition. We analyze the pathways of the different inducers that lead to this cascade. Several actors in the mitogenic signal transduction are required irrespective of the initial signal although their functions may differ: for example members of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3K) cascades. As some of these proteins are also involved in the cell survival mechanisms, they appear to be good targets for therapeutic intervention. In the case of the estrogen-dependent cells, complex interplay between the estrogen receptor (a conditional transcription factor), co-repressors and co-activators offers additional molecular targets for therapy. Besides, we have found that p21(WAF1), an inhibitor of cyclin-dependent kinases, can orient the cell to either proliferation or differentiation suggesting that at an early stage of BC development it may be possible to reverse the cellular changes associated with malignant transformation.

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Section: Therapy Addressing Targets Other Than Er Progestagensmentioning

confidence: 99%

Proliferation of Breast Cancer Cells: Regulation, Mediators, Targets for Therapy

Mešter¹,

Redeuilh²

2008

ACAMC

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“…A variety of endocrine therapies, both surgical and pharmacological, aimed at preventing the estrogen action have been attempted in these diseases [1,2]. Among them, antagonism at the level of the estrogen receptors and inhibition of estrogen synthesis represent the most direct approaches currently adopted in post-menopausal women.…”

Section: Introductionmentioning

confidence: 99%

Pharmacological profile of MEN 11066, a novel potent and selective aromatase inhibitor

Muratori

Lippi

Mancina

et al. 2003

The Journal of Steroid Biochemistry and Molecular Biology

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MEN 11066 is a new non-steroidal compound which potently inhibits human placenta (K i = 0.5 nM) and rat ovarian (K i = 0.2 nM) aromatase in vitro. In vivo, a single oral dose of 0.3 mg kg −1 significantly decreased uterus weight in immature rats after stimulation of uterus growth by androstenedione. MEN 11066 reduced in a dose-dependent manner plasma estradiol levels in adult female rats treated with pregnant mare serum gonadotropin (PMSG). After 2 weeks of repeated daily treatment in adult rats, a significant decrease in uterine weight was observed together with a 65% decrease in plasma estradiol, whereas plasma levels of testosterone, progesterone, aldosterone, corticosterone, cholesterol, LH and FSH were not affected. The lack of any effect by MEN 11066 on adrenal steroids was confirmed by the unchanged plasma corticosterone and aldosterone levels in immature rats and also in adult rats when the repeated treatment with MEN 11066 (15 days) was followed by the administration of a synthetic ACTH analogue. No change in 11␤-hydroxylase or 21-hydroxylase activities was produced in vitro by the addition of 10 M MEN 11066. Fifteen-day treatment with MEN 11066 did not produce changes in several rat hepatic enzymatic activities involved in the metabolism of xenobiotics. These results demonstrated that MEN 11066 is a potent inhibitor of aromatase which does not interfere with the cytochrome P450 involved in the synthesis of other steroids or in the metabolism of xenobiotics.

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Somatostatin and Opioid Receptors in Mammary Tissue

Hatzoglou

Bakogeorgou

Kampa

et al.

Advances in Experimental Medicine and Biology

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Somatostatin and opioid systems, are the two main inhibitory systems in mammals. Both classes of substances have been identified in normal and malignant mammary gland, as well as their cognitive receptors. They have been implied in the inhibition of cell growth of cancer cells and cell lines, in a dose-dependent and reversible manner. Somatostatin acts through homologous receptors (SSTRs), belonging to five distinct classes (SSTR1-5). We, and others have identified SSTR2 and 3 as been the only SSTRs present in the breast. Furthermore, opioids act through the three classes of opioid receptors (mu, delta,kappa). In the breast, kappa opioid receptor subtypes (kappa 1-kappa 3) are the most widely expressed. We further have shown that opioids, in addition to their binding to opioid receptors, compete for binding to SSTRs. This functional interaction, together with other identified modes of opioid action in the breast (modulation of steroid receptors, proteases' secretion, interaction with cytoskeletal elements), will be discussed, taking into consideration also the possible local production of casomorphins (casein-derived opioids), which are very potent antiproliferative agents.

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Novel Endocrine Therapies in Breast Cancer

Cited by 6 publications

References 59 publications

Proliferation of Breast Cancer Cells: Regulation, Mediators, Targets for Therapy

Proliferation of Breast Cancer Cells: Regulation, Mediators, Targets for Therapy

Pharmacological profile of MEN 11066, a novel potent and selective aromatase inhibitor

Somatostatin and Opioid Receptors in Mammary Tissue

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