Gómez-Navarro J, Siegal G P, Alvarez R D, Curiel D T
Gene Therapy Program, Comprehensive Cancer Center, University of Alabama at Birmingham, 35233, USA.
Am J Clin Pathol. 1998 Apr;109(4):444-67. doi: 10.1093/ajcp/109.4.444.
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.
总体而言，对癌症分子基础的描绘，尤其是卵巢癌的分子基础，为出于治疗目的在分子水平进行特异性干预提供了可能性。为此，已开发出三种主要方法：突变补偿、分子化疗和基因免疫增强。针对这些概念性方法中的每一种，包括针对卵巢癌的特定方法在内的人类临床方案已进入I期临床试验，以评估剂量递增、安全性和毒性问题。然而，在这些方法能够成为治疗癌症的有效且常见策略之前，仍有重大问题有待解决。在这方面，对卵巢癌基因治疗应用的研究可以例证基因治疗发展过程中所观察到的合理性和问题，并可能说明正在完善的解决这些问题的前景，包括我们实验室目前的努力。一个首要障碍是将治疗性基因定量且特异性地递送至肿瘤细胞的基本能力。随着载体技术满足这些要求，预计在临床前研究中已观察到的有前景的结果将迅速转化为临床应用，以改善这种威胁女性生命的疾病。
