title: Dysregulation of apoptotic signaling in cancer: molecular mechanisms and therapeutic opportunities.
abstract: Apoptosis is a tightly regulated cell suicide program that plays an essential role in the maintenance of tissue homeostasis by eliminating unnecessary or harmful cells. Defects in this native defense mechanism promote malignant transformation and frequently confer chemoresistance to transformed cells. Indeed, the evasion of apoptosis has been recognized as a hallmark of cancer. Given that multiple mechanisms function at many levels to orchestrate the regulation of apoptosis, a multitude of opportunities for apoptotic dysregulation are present within the intricate signaling network of cell. Several of the molecular mechanisms by which cancer cells are protected from apoptosis have been elucidated. These advances have facilitated the development of novel apoptosis-inducing agents that have demonstrated single-agent activity against various types of cancers cells and/or sensitized resistant cancer cells to conventional cytotoxic therapies. Herein, we will highlight several of the central modes of apoptotic dysregulation found in cancer. We will also discuss several therapeutic strategies that aim to reestablish the apoptotic response, and thereby eradicate cancer cells, including those that demonstrate resistance to traditional therapies.
authors.affiliation: Department of Pathology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Plati
authors.forename: Octavian
authors.initials: O
authors.lastname: Bucur
authors.forename: Roya
authors.initials: R
authors.lastname: Khosravi-Far
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D015398:Signal Transduction
chemical_list: D051017:Apoptosis Regulatory Proteins