Mulshine J L, Johnson B E, Gazdar A F, Shaw G L, Kramer B S, Mitsudomi T, Minna J D, Pass H, Phelps R, Ghosh B
Biomarkers and Prevention Research Branch, National Cancer Institute, National Institutes of Health, Rockville, MD 20850-3300.
Lung Cancer. 1994 Mar;10 Suppl 1:S73-81. doi: 10.1016/0169-5002(94)91669-1.
Consideration of a range of clinical and basic studies conducted at the National Cancer Institute which explore the nature of the tumor biology of lung identify the limitations of using chemotherapy for the treatment of advanced lung cancer. No single mechanistic explanation for lung cancer's chemoresistance is apparent, although considerable information about the biology of lung cancer and some of its clinical consequences have been elucidated. In contrast to previous works from our group, this presentation will focus principally on studies of the nature of drug resistance with non-small cell cancer. An alternative combined modality strategy for lung cancer control is to focus on epithelial progression of lung cancer using local modalities while it is still confined to the bronchial epithelium. Particular high risk populations may be appropriate to determine if local tools such as photodynamic laser therapy can be effective in this application. To deal with the underlying biochemical perturbations resulting from critical exposure of the bronchial epithelium to carcinogens, rational biochemical intervention with 13 cis retinoic acid are being evaluated in several clinical trials. An evolution towards more effective lung cancer control may involve the combined modalities of laser ablation of accessible dysplastic epithelium and chronic administration of intervention agents, such as retinoids, to neutralize cancer promotion dynamics in the more remote areas of the lung epithelium.
美国国立癌症研究所开展了一系列临床和基础研究，探讨肺癌肿瘤生物学的本质，结果表明使用化疗治疗晚期肺癌存在局限性。尽管已经阐明了关于肺癌生物学及其一些临床后果的大量信息，但对于肺癌化疗耐药性，尚无单一的机理解释。与我们团队之前的研究不同，本次报告将主要聚焦于非小细胞癌耐药性本质的研究。肺癌控制的另一种联合治疗策略是，在肺癌仍局限于支气管上皮时，利用局部治疗手段关注肺癌的上皮进展。对于特定的高风险人群，确定诸如光动力激光治疗等局部治疗手段在此应用中是否有效可能是合适的。为应对支气管上皮因接触致癌物而产生的潜在生化紊乱，正在多项临床试验中评估使用13-顺式维甲酸进行合理的生化干预。朝着更有效的肺癌控制方向发展，可能涉及对可触及的发育异常上皮进行激光消融，并长期给予干预药物（如维甲酸），以中和肺上皮更远处区域的癌症促进动态变化。
