Defects of the apoptotic pathway as therapeutic target against cancer.
Over the past 10 years evidence has been accumulating that antitumour agents induce apoptosis in cancer cells and that abnormalities in apoptosis signaling pathways often occur in cancer cells and are associated with drug resistance. The implication is that factors regulating the apoptotic process play a critical role in tumour sensitivity to chemotherapy, and hence may be rational molecular targets for novel antitumour agents. Significantly, oncogenic signals make cancer cells intrinsically more susceptible to apoptosis; defects in the pathway occur subsequent to cancer development. Important emerging questions are the pattern of alterations in the apoptotic pathway in a particular tumour (cell) and the best strategy to exploit them and induce selective tumour cell death. Here, we review recent progress in this field.
Mashima
Tetsuo
T
Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
Tsuruo
Takashi
T
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use; D053148:Caspase 3 / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D020536:Enzyme Activators / Q000494:pharmacology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics*; D009596:Nitrophenols / Q000494:pharmacology / Q000627:therapeutic use; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use; D014226:Triazenes / Q000494:pharmacology
C501332:ABT-737; D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D020536:Enzyme Activators; D051034:Inhibitor of Apoptosis Proteins; D009596:Nitrophenols; D016376:Oligonucleotides, Antisense; D010879:Piperazines; D019253:Proto-Oncogene Proteins c-bcl-2; D011725:Pyridines; D013449:Sulfonamides; D014226:Triazenes; C470638:alpha-(trichloromethyl)-4-pyridineethanol; C034613:triacsin C; D053148:Caspase 3