Roth J A, Swisher S G, Merritt J A, Lawrence D D, Kemp B L, Carrasco C H, El-Naggar A K, Fossella F V, Glisson B S, Hong W K, Khurl F R, Kurie J M, Nesbitt J C, Pisters K, Putnam J B, Schrump D S, Shin D M, Walsh G L
Department of Thoracic and Cardiovascular Surgery, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Semin Oncol. 1998 Jun;25(3 Suppl 8):33-7.
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.
确定导致正常细胞恶变的基因损伤，为我们提供了将这些损伤作为治疗靶点的机会。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之间的关联证据，进行p53替代治疗是针对该疾病的一种合理治疗方法。在一项I期研究中，给21例晚期非小细胞肺癌患者施用腺病毒p53载体（Adp53），毒性很小。每月间隔进行多达6次瘤内注射耐受性良好。p53转基因的表达明显，同时伴有潜在的有益临床反应。用Adp53治疗的指示病变的疾病进展时间似乎因更高剂量的载体、顺铂联合治疗以及肿瘤活检标本上的凋亡证据而延长。现在应该进行II期试验以确定对Adp53的反应率。
