p53 Gene Therapy

摘要: Based on the frequent inactivation of p53 gene product in human malignancy, and its functional involvement tumor suppression, cell cycle control apoptosis, was identified as an attractive target for somatic therapy strategies cancer. Several pilot phase I studies explored intratumoral injection viral expression vectors encoding cDNA patients with advanced These confirmed safety feasibility this approach. Further, vector-specific transgene surrogate markers biological activity were demonstrated. Local regression, or stabilization growth, observed some studies, interpreted evidence clinical activity. No formal assessment vivo transduction efficacy vector distribution, following vectors, performed. The instillation adenoviral into cavitary organs, such peritoneum bladder, has been studied alternative mode application. Intravesical installation, combination a transduction-enhancing agent, proved to be safe, feasible biologically active study bladder Transgene expression, superior trial, effective distribution penetration achieved by former treatment. publication results from intraperitoneal installation ovarian cancer is still awaited. To date, only one published II formally assessed adenovirus-mediated transfer non-small lung (NSCLC). clinically relevant benefit local undergoing systemic chemotherapy when responses individual lesions treated compared. additional performed NSCLC head neck are pending. In summary, current failed translate preclinical success clinic. A major obstacle unknown, probably inefficient, delivery injection. contrast, can intravesical merit further investigation studies. Recent improvements technology, including targeting techniques, tissue-specific andtumor-selective replication, will certainly allow investigators next wave carefully conducted trials.