Gene therapy in brain tumours: implications of the size of glioblastoma on its curability.
The authors have used the thymidine kinase/ganciclovir system to block glioblastoma multiforme neoplastic cells in vivo, both in experimental animals and in two patients in which the more conventional therapies had been unsuccessful. In the Wistar rat it was found that the curability potential of the system is correlated with tumoral volume. Tumours smaller than 20 mm3 can be cured with defective retrovirus that do not carry the Herpes simplex thymidine kinase (Hsvtk) gene. While tumours smaller than 150 mm3 can regress totally by the kinase/ganciclovir system, those above that size cannot be cured by this treatment. In humans the situation seems very similar in that the authors have been unable either to reduce the tumour size of recurrent patients with tumour volumes larger than 100 cm2 applying the standard thymidine kinase/ganciclovir gene therapy or to prolong their survival time more than 8 months [7]. When a combination of size reduction by neurosurgery and gene therapy was used the survival time increased considerably. Two patients have been treated by partial surgery and repeated treatment with thymidine kinase/ganciclovir through an Ommaya reservoir connected to a catheter leading into the tumour cavity. The magnetic resonance imaging (MRI) of these patients show only a residual tumoral growth along side the tumoral bed. The procedure may be partially controlling the proliferation of cancerous cells, because, these two patients having recurrent glioblastoma, are alive 11 and 17 months after the beginning of the treatment.
Izquierdo
M
M
Departamento de Biologia Molecular/Centro de Biología Molecular Severo Ochoa, Facultad de Ciencias, Universidad Autónoma de Madrid, Cantoblanco, Spain.
Cortés
M L
ML
Martín
V
V
de Felipe
P
P
Izquierdo
J M
JM
Pérez-Higueras
A
A
Paz
J F
JF
Isla
A
A
Blázquez
M G
MG
D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016923:Cell Death / Q000235:genetics; D003131:Combined Modality Therapy; D015774:Ganciclovir / Q000008:administration & dosage; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005909:Glioblastoma / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008297:Male; D051379:Mice; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology / Q000628:therapy; D009368:Neoplasm Transplantation; D011379:Prognosis; D051381:Rats; D017208:Rats, Wistar; D018139:Simplexvirus / Q000235:genetics; D015996:Survival Rate; D013937:Thymidine Kinase / Q000235:genetics; D014407:Tumor Cells, Cultured
D013937:Thymidine Kinase; D015774:Ganciclovir