[Glioblastomas are resistant to apoptosis but less resistant to the autophagic process].
Malignant gliomas of which glioblastomas represent the ultimate grade of malignancy are characterized by dismal prognoses because malignant glioma cells present both important proliferation and neoangiogenesis processes and can actively migrate through the narrow extra-cellular spaces in the brain, often travelling relatively long distances, making them elusive targets for effective surgical management. Invasive malignant glioma cells show a decrease in their proliferation rates and a relative resistance to apoptosis (type I programmed cell death) but seem less resistant to autophagic cell death (type II programmed cell death). Autophagic cell death represents an alternative mechanism to overcome, at least partly, the dramatic resistance of glioblastomas to pro-apoptotic-related therapies. Another way to potentially overcome apoptosis resistance is to decrease the migration of malignant glioma cells in the brain, which then should restore a level of sensitivity to pro-apoptotic drugs. We conclude this work with an algorithm showing the optimal current treatment for glioblastoma with the potent future innovations.
Lefranc
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Service de Neurochirurgie, Hôpital Erasme, Institut de Pharmacie, ULB.
D000465:Algorithms; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D002465:Cell Movement; D002986:Clinical Trials as Topic; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D005544:Forecasting; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D006801:Humans; D011379:Prognosis; D020123:Sirolimus / Q000494:pharmacology / Q000627:therapeutic use; D000077204:Temozolomide; D014157:Transcription Factors
D000903:Antibiotics, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D014157:Transcription Factors; D003606:Dacarbazine; D020123:Sirolimus; D000077204:Temozolomide