title: Emerging targeted therapies in triple-negative breast cancer.
abstract: Standard chemotherapy regimens can prove effective for patients with early triple-negative breast cancer (TNBC); however, patients with advanced disease typically respond poorly and rapidly progress, and the outcome is poor. New targeted therapies are therefore an urgent unmet medical need for this patient population. Translational and clinical studies into new TNBC treatments have been facilitated by the increased understanding of the aberrant signal transduction pathways regulating growth and survival and the development of chemoresistance in TNBC. Some of the established targeted agents that have been approved in other indications may prove beneficial to patients with TNBC; however, in the absence of approved targeted agents for the treatment of TNBC, most new agents remain experimental. Increased understanding of molecular profiles of TNBC subtypes is likely to improve therapeutic strategies with targeted agents. Novel strategies have reached clinical evaluation in patients with TNBC, including targeting angiogenesis vascular endothelial growth factor and proliferation signalling (receptor tyrosine kinases and mammalian target of rapamycin). Aggressive TNBCs have been found to associate closely with BRCA1 mutation or dysregulation. The recent development of new investigational agents targeting DNA repair, either directly with poly(adenosine disphosphate-ribose) polymerase inhibitors or indirectly through DNA-binding or DNA-damage potentiation, is a major focus of current clinical studies. These and other targeted therapies represent a new approach to TNBC therapy.
authors.affiliation: St Vincent's University Hospital, Dublin, Ireland. john.crown@icorg.ie
authors.forename: J
authors.initials: J
authors.lastname: Crown
authors.forename: J
authors.initials: J
authors.lastname: O'Shaughnessy
authors.forename: G
authors.initials: G
authors.lastname: Gullo
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy; D011064:Poly Adenosine Diphosphate Ribose / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: D011064:Poly Adenosine Diphosphate Ribose; D011505:Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D040262:Receptors, Vascular Endothelial Growth Factor; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human; C508053:ERBB2 protein, human