Gene therapy: ovarian carcinoma as the paradigm.

The delineation of the molecular basis of cancer in general, and of ovarian carcinoma in particular, allows for the possibility of specific intervention at the molecular level for therapeutic purposes. To this end, three main approaches have been developed: mutation compensation, molecular chemotherapy, and genetic immunopotentiation. For each of these conceptual approaches, human clinical protocols, including those specific for ovarian carcinoma, have entered phase I clinical trials to assess dose escalation, safety, and toxicity issues. However, major problems remain to be solved before these approaches can become effective and commonplace strategies for the treatment of cancer. In this regard, an examination of the applications of gene therapy for ovarian carcinoma can exemplify the rationality and the problems observed in the development of gene therapy, and may illustrate prospects for their solution that are being refined, including current efforts in our laboratory. An overriding obstacle is the basic ability to deliver therapeutic genes quantitatively, and specifically, into tumor cells. As vector technology fulfills these requirements, it is anticipated that promising results already observed in preclinical studies will translate quickly into the clinical setting for amelioration of this life-threatening disease in women.