Use of Safety-Modified Retroviruses to Introduce Chemotherapy Resistance Sequences into Normal Hematopoietic Cells for Chemoprotection During the Therapy of Breast Cancer: A Pilot Trial. M.D. Anderson Cancer Center, Houston, Texas

Results of MDR-1 vector modification trial indicate that granulocyte/macrophage colony-forming unit cells do not contribute to posttransplant hematopoietic recovery following intensive systemic therapy

“…The MDR-1 genetic chemoprotection trials were as described (8,9). Patients who relapsed after surgery who were then only partially responsive to salvage conventional dose chemotherapy were exposed to conventional dose chemotherapy as follows: for ovarian cancer patients, 180 mg͞m 2 VP16 (etoposide) as an intravenous bolus administration (IVB) once a day (qd) for 5 days and 600 mg͞m 2 cyclophosphamide IVB qd for 5 days; for breast cancer patients, a single dose of 4 g͞m 2 cyclophosphamide IVB.…”

Retroviral transfer and long-term expression of human cytidine deaminase cDNA in hematopoietic cells following transplantation in mice

“…Clinical trials on chemoprotection of cancer patients with the introduction of the MDR gene into hematopoietic progenitor cells are presently under investigation. [8][9][10][11] Our laboratory has been investigating the drug resist-ance gene, cytidine deaminase (CD), which codes for an enzyme that inactivates cytosine nucleoside analogues, such as cytosine arabinoside (Ara-C), 2Ј,2Ј-difluorodeoxycytidine (dFdC) and 5-aza-2Ј-deoxycytidine (5-AZA-CdR). 12,13 Myelosuppression constitutes a major limiting factor for the utilization of high doses of these analogues in cancer therapy.…”

Gene therapy for cancer-in the dock, blown off course or full speed ahead?

“…Indeed, cancer was the catalyst by which the concept of gene therapy became expanded to include therapy via delivery of genetic material other than just corrective genes [17]. Hence, delivery of antisense molecules (directed against activated oncogenes or growth factors) [18], cytotoxic genes (in readiness for prodrug activation) [19], immunostimulatory genes (for the activation of anti-tumour immune responses) [20] and chemoprotective genes (for increased dosing of chemotherapy) [21] are all now routinely classified as gene therapy. It is a critical examination of the potential of these approaches which forms the basis of this issue of Cancer Metastasis Reviews (Chapters 2q5].…”