title: Targeting the mitochondrial apoptotic pathway: a preferred approach in hematologic malignancies?
abstract: Acquired resistance toward apoptosis represents one of the hallmarks of human cancer and a major cause of the inefficacy of most anticancer treatment regimens. Based on its ability to inhibit apoptosis, the B-cell lymphoma/leukemia 2 (Bcl-2) protein family has garnered the most attention as a promising therapeutic target in cancer. Accordingly, efforts have lately been focused on the development of drugs targeting Bcl-2 proteins with considerable therapeutic success, particularly in hematologic malignancies. Here, we review the previous studies and highlight the pivotal role of the Bcl-2 protein family in the homeostasis of hematologic tissue compartment. This knowledge provides more insight into why some cancers are more sensitive to Bcl-2 targeting than others and will foster the clinical evaluation of Bcl-2-targeting strategies in cancer by avoiding severe on-target side effects in the development of healthy tissues.
authors.affiliation: 1] Centre for Molecular Medicine Cologne (CMMC), Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Köln, Germany [2] Institute for Medical Microbiology, Immunology and Hygiene (IMMIH), University of Cologne, Köln, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Brinkmann
authors.affiliation: 1] Centre for Molecular Medicine Cologne (CMMC), Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Köln, Germany [2] Institute for Medical Microbiology, Immunology and Hygiene (IMMIH), University of Cologne, Köln, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Kashkar
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D015195:Drug Design; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D058990:Molecular Targeted Therapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2