Cross-talk between estrogen receptor and growth factor pathways as a molecular target for overcoming endocrine resistance.
Introduced more than 100 years ago, endocrine therapy is still the most important systemic therapy for all stages of estrogen receptor (ER) -positive breast tumors. A major clinical problem limiting the usefulness of this therapy is tumor resistance, either de novo or acquired during the course of the treatment. Relatively new discoveries emphasize the complexity of ER signaling and its multiple regulatory interactions with growth factor and other kinase signaling pathways. Both genomic (nuclear) and nongenomic (membrane and cytoplasmic) ER activities contribute to this intimate cross-talk, which is probably a fundamental factor in endocrine resistance. New targeted therapies, especially against the epidermal growth factor receptor/HER-2 pathway, should be carefully evaluated in more (bio)logical strategies to enable them to be exploited appropriately. A strategy of combining endocrine therapy (particularly tamoxifen) with these inhibitors, to circumvent de novo and acquired resistance, will be discussed. We will also emphasize open questions and future challenges in the dynamic research field of molecular ER biology from the endocrine therapy perspective.
Schiff
Rachel
R
Breast Center, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA. rschiff@breastcenter.tmc.edu
Massarweh
Suleiman A
SA
Shou
Jiang
J
Bharwani
Lavina
L
Mohsin
Syed K
SK
Osborne
C Kent
CK
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism*; D011485:Protein Binding; D020239:Receptor Cross-Talk; D011960:Receptors, Estrogen / Q000378:metabolism*; D015398:Signal Transduction
D018931:Antineoplastic Agents, Hormonal; D006133:Growth Substances; D011960:Receptors, Estrogen; D066246:ErbB Receptors