Gene therapy for non-small cell lung cancer: a preliminary report of a phase I trial of adenoviral p53 gene replacement.
Gene therapy for non-small cell lung cancer: a preliminary report of a phase I trial of adenoviral p53 gene replacement.
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发表时间：
1998-06
影响因子：
4
通讯作者：
J. Roth;S. Swisher;J. Merritt;D. Lawrence;B. Kemp;C. H. Carrasco;A. El-Naggar;F. Fossella;B. Glisson;W. Hong;F. R. Khurl;J. Kurie;J. Nesbitt;K. Pisters;J. Putnam;D. Schrump;D. Shin;G. Walsh
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作者：
J. Roth;S. Swisher;J. Merritt;D. Lawrence;B. Kemp;C. H. Carrasco;A. El-Naggar;F. Fossella;B. Glisson;W. Hong;F. R. Khurl;J. Kurie;J. Nesbitt;K. Pisters;J. Putnam;D. Schrump;D. Shin;G. Walsh
鉴定导致正常细胞恶性的遗传病变为我们提供了靶向这些病变作为治疗手段的机会。鉴于肿瘤抑制基因p53在细胞周期调控和细胞凋亡中发挥的关键作用，以及p53突变与非小细胞肺癌相关的证据，尝试p53替代是治疗这种疾病的合理方法。在一项I期研究中，对21名晚期非小细胞肺癌患者给予腺病毒p53载体（Adp53）几乎没有产生毒性。每月间隔最多6次瘤内注射耐受性良好。p53转基因的表达是明显的，沿着潜在有用的临床反应。用Adp53治疗的指示病变中的疾病进展时间似乎通过较高剂量的载体、伴随的顺铂治疗和肿瘤活检标本上的细胞凋亡证据而增强。现在应该进行II期试验以确定对Adp53的应答率。
The identification of genetic lesions that lead a normal cell to become malignant presents us with the opportunity of targeting those lesions as a means of therapy. Given the key role played by the tumor suppressor gene p53 in cell cycle regulation and apoptosis, and the evidence linking p53 mutations with non-small cell lung cancer, attempts at p53 replacement are a logical approach to therapy in this disease. In a phase I study, administration of an adenoviral p53 vector (Adp53) to 21 patients with advanced non-small cell lung cancer produced little toxicity. Up to six intratumoral injections at monthly intervals were well-tolerated. Expression of the p53 transgene was evident, along with potentially useful clinical responses. Time to disease progression in the indicator lesion treated with Adp53 appears to be enhanced by higher doses of vector, concomitant cisplatin therapy, and evidence of apoptosis on tumor biopsy specimens. Phase II trials should now be undertaken to determine the response rate to Adp53.