Retinoids and breast cancer: new clues to increase their activity and selectivity

All-trans retinoic acid and derivatives (retinoids) are promising agents in the management of certain hematologic malignancies and solid tumors, including breast cancer. Retinoids are endowed with anti-proliferative, cyto-differentiating and apoptotic effects that are largely mediated by activation of the nuclear hormone retinoic acid receptors RARα, RARβ and RARγ. These are ligand-dependent transcriptional factors controlling the expression of numerous genes. The relative importance of each receptor subtype for the anti-tumor activity of retinoids is largely unknown. Clarification of this point is of fundamental importance for the rational design of retinoid-based therapeutic approaches aimed at controlling a heterogeneous type of tumors, like breast cancer.

[1]  G. Goodall,et al.  Induction of miR-21 by Retinoic Acid in Estrogen Receptor-positive Breast Carcinoma Cells , 2010, The Journal of Biological Chemistry.

[2]  Min Lu,et al.  Expression of estrogen receptor α, retinoic acid receptor α and cellular retinoic acid binding protein II genes is coordinately regulated in human breast cancer cells , 2005, Oncogene.

[3]  P Ubezio,et al.  Synergistic antitumor activity of lapatinib and retinoids on a novel subtype of breast cancer with coamplification of ERBB2 and RARA , 2012, Oncogene.

[4]  M. Hallett,et al.  Stromal retinoic acid receptor β promotes mammary gland tumorigenesis , 2010, Proceedings of the National Academy of Sciences.

[5]  T. Barbui,et al.  AM580, a stable benzoic derivative of retinoic acid, has powerful and selective cyto-differentiating effects on acute promyelocytic leukemia cells. , 1996, Blood.

[6]  E Marubini,et al.  Fifteen-year results of a randomized phase III trial of fenretinide to prevent second breast cancer. , 2006, Annals of oncology : official journal of the European Society for Medical Oncology.

[7]  E. Garattini,et al.  Retinoids as differentiating agents in oncology: a network of interactions with intracellular pathways as the basis for rational therapeutic combinations. , 2007, Current pharmaceutical design.

[8]  Min Lu,et al.  Expression of estrogen receptor alpha, retinoic acid receptor alpha and cellular retinoic acid binding protein II genes is coordinately regulated in human breast cancer cells. , 2005, Oncogene.

[9]  M. Calzi,et al.  AM 580 , a Stable Benzoic Derivative of Retinoic Acid , Has Powerful and Selective Cyto-Differentiating Effects on Acute Promyelocytic Leukemia Cells , 2002 .

[10]  E. Garattini,et al.  Cytodifferentiation by retinoids, a novel therapeutic option in oncology: rational combinations with other therapeutic agents. , 2007, Vitamins and hormones.

[11]  T. Schug,et al.  Opposing Effects of Retinoic Acid on Cell Growth Result from Alternate Activation of Two Different Nuclear Receptors , 2007, Cell.

[12]  Jack Cuzick,et al.  Preventive therapy for breast cancer: a consensus statement. , 2011, The Lancet. Oncology.

[13]  T. Schug,et al.  Overcoming retinoic acid-resistance of mammary carcinomas by diverting retinoic acid from PPARβ/δ to RAR , 2008, Proceedings of the National Academy of Sciences.

[14]  Lorenzo Ferraro,et al.  Estrogen receptor alpha controls a gene network in luminal-like breast cancer cells comprising multiple transcription factors and microRNAs. , 2010, The American journal of pathology.

[15]  Charles M. Perou,et al.  Practical implications of gene-expression-based assays for breast oncologists , 2012, Nature Reviews Clinical Oncology.

[16]  M. Dawson,et al.  Reversal by RARα agonist Am580 of c-Myc-induced imbalance in RARα/RARγ expression during MMTV-Myc tumorigenesis , 2012, Breast Cancer Research.

[17]  Zhu Chen,et al.  Acute promyelocytic leukaemia: novel insights into the mechanisms of cure , 2010, Nature Reviews Cancer.