Management Problems in Oncology
Man has evolved sophisticated defence mechanisms over millions of years to combat insertion of foreign DNA into his cells. However, gene therapy carries huge potential for the treatment of cancer. The challenge is therefore to translate our scien-tific kn
- PDF / 231,820 Bytes
- 8 Pages / 468 x 720 pts Page_size
- 109 Downloads / 214 Views
MANAGEMENT PROBLEMS IN ONCOLOGY Susan J. Cleator and Pat Price Department of Clinical Oncology Hammersmith Hospital London
1. INTRODUCTION Gene therapy is the introduction of nucleic acids into cells for the purpose of treating disease. Over the last decade the molecular basis of many sporadic and familial tumours has been elucidated. The development of the malignant phenotypes occurs as a result of loss of expression of recessive tumour suppressor genes and aberrant expression of dominant oncogenes. Somatic mutations tend to arise sequentially, with or without a predisposing germ line mutation. Research in this field has been parallelled by advances in the technology of mammalian gene transfer. This has enabled us to attempt to treat cancer at the molecular level.
1.1. Human Disease Models The lead candidates for gene therapy are well-defined, monogenic diseases such as cystic fibrosis or adenosine deaminase deficiency which could be corrected, in principle, by replacing the “missing” gene. Much of the early gene therapy work focused on these diseases. However, most currently approved gene therapy protocols concern treatment of cancer. This approach can be readily tested in cancer patients and there is a recognised need for a novel treatment in this disease.
1.2. Gene Therapy Strategies In principle, we could aim to develop strategies of either restoring tumour suppressor gene function or down-regulating oncogenic expression. However, carcinogenesis is generally a multistep process with multiple mutations. It would not be possible to identify and correct all the resultant abnormalities and gene function would need to be restored in all cells. These problems have led to the development of other strategies including the introduction of genes which (i) stimulate an immune response, (ii) which Cancer Gene Therapy: Past Achievements and Future Challenges, edited by Habib Kluwer Academic/Plenum Publishers, New York, 2000.
3
4
S. J. Cleator and P. Price
convert an inactive prodrug to an active toxin or (iii) which can render marrow stem cells resistant to chemotherapy drugs. Interest is growing in using gene therapy to interfere with tumour angiogenesis.
1.3. Gene Delivery The success of gene therapy rests on our being able to insert genes into cells with sufficient efficiency and accuracy. Current approaches generally employ a vector. Broadly speaking there are two approaches to gene insertion, (i) Ex vivo techniques involve transducing target cells in vitro with a gene. These cells are then rendered replication incompetent and are then transplanted into the recipient. (ii) In vivo techniques introduce the vector directly into target tissue. Systemic injection of gene-bearing vector represents an attractive means of targeting disseminated disease, although it presents technical problems.
2. PROBLEMS WITH EXISTING ANTICANCER TREATMENT Standard anticancer treatments include surgery, radiation and chemotherapy. These can be effective if disease is localised or if the disease is sensitive to treatment e.g. lymphom
Data Loading...
