Sequential treatment of drug-resistant tumors with targeted minicells containing siRNA or a cytotoxic drug

• Published in: Nature biotechnology Vol. 27; no. 7; pp. 643 - 651
• Main Authors: Brahmbhatt, Himanshu, MacDiarmid, Jennifer A, Amaro-Mugridge, Nancy B, Madrid-Weiss, Jocelyn, Sedliarou, Ilya, Wetzel, Stefanie, Kochar, Kartini, Brahmbhatt, Vatsala N, Phillips, Leo, Pattison, Scott T, Petti, Carlotta, Stillman, Bruce, Graham, Robert M
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.07.2009; Nature Publishing Group
• Subjects: Agriculture; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacokinetics; ATP Binding Cassette Transporter, Subfamily B, Member 1 - biosynthesis; ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism; Bioinformatics; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering/Biotechnology; Biomedicine; Biotechnology; Cancer; Care and treatment; Cell Cycle Proteins - genetics; Cell Line, Tumor; Cell- and Tissue-Based Therapy - methods; Cellular biology; Chemotherapy; Drug Delivery Systems - methods; Drug resistance; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug therapy; Female; Fundamental and applied biological sciences. Psychology; Gene Knockdown Techniques; Genetic aspects; HCT116 Cells; Health. Pharmaceutical industry; Heterogeneity; Humans; Industrial applications and implications. Economical aspects; Life Sciences; Mice; Mice, Nude; Microscopy, Fluorescence; Miscellaneous; Neoplasms - drug therapy; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - therapy; Polo-Like Kinase 1; Protein Serine-Threonine Kinases - genetics; Proto-Oncogene Proteins - genetics; Ribonucleic acid; RNA; RNA, Small Interfering - administration & dosage; RNA, Small Interfering - genetics; Salmonella typhimurium - physiology; Toxicity; Tumors; Xenograft Model Antitumor Assays; Australia; United States; Antineoplastic agent; Drug; Resistance; Delivery system; Gene silencing; RNA interference; Treatment; Targeting; Tumor; siRNA; Minicell; Cancer

Drug resistance remains a major hurdle to effective cancer chemotherapy. MacDiarmid et al . show that bacterially derived minicells packaged with siRNAs reverse tumor drug resistance and that subsequent treatment with minicells loaded with cytotoxic drugs causes tumor stabilization or regression. Th...