title: Developmental pathways in breast cancer and breast tumor-initiating cells: therapeutic implications.
abstract: The recognition of breast cancer as a molecularly heterogeneous disease where individual tumors display cellular hierarchy containing "primitive" stem-like tumor-initiating cells (TICs) and their derivatives, has directed efforts towards the development of personalized targeted therapies based on the characteristics of individual cancers. Targeted therapies are designed to attack processes that uniquely support cancer progression, including maintenance of TICs, invasion, metastasis, cell survival and tumor-related angiogenesis and thereby result in less collateral damage than conventional chemotherapy. Recently, it has been demonstrated that pathways such as Hedgehog (Hh), Wnt and Notch, which regulate development during embryonic life and somatic stem cells (SCs) in the adult organism, can be reactivated in malignancies and support the TIC compartment. Herein, we review the role of developmental pathways in stem cell biology and provide an up-to-date survey of pre-clinical and clinical trials of novel strategies to target them.
authors: Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, 620 University Avenue, Toronto, Ontario, Canada M5G 2M9.
authors: Julia
authors: J
authors: Izrailit
authors: Michael
authors: M
authors: Reedijk
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D005260:Female; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051881:Receptor, Notch1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051155:Wnt1 Protein / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D053823:Hedgehog Proteins; D051881:Receptor, Notch1; D051155:Wnt1 Protein