Education And Debate

Personal paper: Gene therapy for cancer—managing expectations

BMJ 1997; 315 doi: https://doi.org/10.1136/bmj.315.7122.1604 (Published 13 December 1997) Cite this as: BMJ 1997;315:1604
  1. Alan A Melcher, MRC clinical training fellowa,
  2. Ignacio Garcia-Ribas, clinical research fellowb,
  3. Richard G Vile, laboratory heada
  1. a Imperial Cancer Research Fund Molecular Oncology Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London W12 0NN
  2. b Imperial Cancer Research Fund/Richard Dimbleby Department of Cancer Research, St Thomas's Hospital, London SE1 7EH
  1. Correspondence to: Dr Vile
  • Accepted 28 May 1997

Introduction

Gene therapy seems to offer new hope in cancer treatment. The new molecular technology can be used to target tumour cells in many ways. These include techniques that correct genes directly—for example, by delivering a nucleic acid sequence that complements and therefore inactivates an oncogene (antisense technology) or by replacing copies of tumour suppressor genes that are often lost in malignant cells. However, the success of these direct approaches is limited because current technology cannot deliver therapeutic genes to all cancer cells. Alternative strategies have been developed using genes that encode proteins, such as cytokines, which can activate the patient's immune response against the tumour. Another application of gene therapy, which is already undergoing extensive clinical trials, is the transduction of tumour cells with so called suicide genes, which encode enzymes that can convert a prodrug to its toxic metabolite.

Despite the diversity of gene therapies for cancer in both the laboratory and clinic, disappointment is emerging that gene therapy has not fulfilled its early promise.1 Since no dramatic clinical success has been reported to date, this criticism cannot be ignored, and an objective reconsideration of the potential of gene therapy is timely.

Gene therapy has failed to live up to expectations so far because these have been unrealistic. A lack of realism can be destructive if it leads to disillusionment. Potential benefits of a new approach may be lost if research is abandoned prematurely because dramatic advances have not been made. In oncology, the excitement engendered by gene therapy has been heightened by the inadequacy of current treatments for many of the common adult cancers.

There are good scientific explanations for the inability of gene therapy to produce impressive cures in cancer, but for an understanding of these, gene therapy must be considered within the context and aims …

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