Bcl-2 family members as molecular targets in cancer therapy.
Escape from apoptosis is often a hallmark of cancer cells, and is associated to chemotherapy resistance or tumor relapse. Proteins from the Bcl-2 family are the key regulators of the intrinsic pathway of apoptosis, controlling the point-of no-return and setting the threshold to engage the death machinery in response to a chemical damage. Therefore, Bcl-2 proteins have emerged as an attractive target to develop novel anticancer drugs. Current pharmacological approaches are focused on the use of peptides, small inhibitory molecules or antisense oligonucleotides to neutralize antiapoptotic Bcl-2 proteins, lowering the threshold and facilitating apoptosis of cancer cells. We discuss here recent advances in the development of Bcl-2 targeted anticancer therapies.
Marzo
Isabel
I
Departamento de Bioquimica y Biologia Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, Pedro Cerbuna, 12, 50009 Zaragoza, Spain. imarzo@unizar.es
Naval
Javier
J
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D051023:BH3 Interacting Domain Death Agonist Protein / Q000187:drug effects / Q000378:metabolism; D001578:Benzopyrans / Q000627:therapeutic use; D001688:Biological Products / Q000627:therapeutic use; D019254:Genes, bcl-2 / Q000187:drug effects* / Q000235:genetics; D006072:Gossypol / Q000627:therapeutic use; D006801:Humans; D007211:Indoles; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy; D009570:Nitriles / Q000627:therapeutic use; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011758:Pyrroles / Q000627:therapeutic use
D000970:Antineoplastic Agents; D051023:BH3 Interacting Domain Death Agonist Protein; D001578:Benzopyrans; D001688:Biological Products; D007211:Indoles; D009570:Nitriles; D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D011758:Pyrroles; C456800:ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate; D006072:Gossypol; C520962:obatoclax