肺癌是*癌癥相關(guān)死亡的主要原因，在過(guò)去的半個(gè)世紀(jì)里，它的死亡率變化不大，大約是20%的存活率。

一種吸入式的雞尾酒化療可能有助于增加肺癌患者的存活，同時(shí)限制有害的副作用。Tamara Minko及其同事設(shè)計(jì)了一種吸入式的化學(xué)療法，它包括了抗癌藥物和設(shè)計(jì)用于抑制與化療抗性有關(guān)基因的化合物，然后讓患有多重人類(lèi)肺癌腫瘤的小鼠接受了這一療法。

這組作者報(bào)告說(shuō)，這種吸入式療法比單獨(dú)使用抗癌藥物或者通過(guò)靜脈注射給藥更成功地殺死了癌細(xì)胞并縮小了腫瘤的尺寸。測(cè)試顯示，與注射相比，吸入藥物的方法增強(qiáng)了藥物與小鼠肺部的接觸，并限制了在其他健康器官的毒性積累。

這組作者說(shuō)，這種療法可能有助于患者克服化療的一些障礙，諸如癌細(xì)胞抗性、藥物在肺部的濃度低，以及不良副作用。

PNAS doi: 10.1073/pnas.1004604107

Inhibition of lung tumor growth by complex pulmonary delivery of drugs with oligonucleotides as suppressors of cellular resistance
Olga B. Garbuzenkoa, Maha Saada, Vitaly P. Pozharova, Kenneth R. Reuhlb,c,d, Gediminas Mainelisc,e, and Tamara Minkoa,c,d,1

Departments of aPharmaceutics,
bPharmacology and Toxicology, and
eEnvironmental Sciences, Rutgers, The State University of New Jersey, Piscataway, NJ 08854; c Environmental and Occupational Health Sciences Institute, Piscataway, NJ 08855; and
d Cancer Institute of New Jersey, New Brunswick, NJ 08903

Development of cancer cell resistance, low accumulation of therapeutic drug in the lungs, and severe adverse treatment side effects represent main obstacles to efficient chemotherapy of lung cancer. To overcome these difficulties, we propose inhalation local delivery of anticancer drugs in combination with suppressors of pump and nonpump cellular resistance. To test this approach, nanoscale-based delivery systems containing doxorubicin as a cell death inducer, antisense oligonucleotides targeted to MRP1 mRNA as a suppressor of pump resistance and to BCL2 mRNA as a suppressor of nonpump resistance, were developed and examined on an orthotopic murine model of human lung carcinoma. The experimental results show high antitumor activity and low adverse side effects of proposed complex inhalatory treatment that cannot be achieved by individual components applied separay. The present work potentially contributes to the treatment of lung cancer by describing a unique combinatorial local inhalation delivery of drugs and suppressors of pump and nonpump cellular resistance.