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10.1371/journal.pone.0200163

http://scihub22266oqcxt.onion/10.1371/journal.pone.0200163
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C6042707!6042707!30001368
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suck abstract from ncbi


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pmid30001368      PLoS+One 2018 ; 13 (7): ä
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  • Downregulation of PIK3CA via antibody-esiRNA-complexes suppresses human xenograft tumor growth #MMPMID30001368
  • Bäumer N; Rehkämper J; Appel N; Terheyden L; Hartmann W; Wardelmann E; Buchholz F; Müller-Tidow C; Berdel WE; Bäumer S
  • PLoS One 2018[]; 13 (7): ä PMID30001368show ga
  • Precision cancer therapy requires on the one hand detailed knowledge about a tumor?s driver oncogenes and on the other hand an effective targeted therapy that specifically inhibits these oncogenes. While the determination of genomic landscape of a tumor has reached a very precise level, the respective therapy options are scarce. The application of small inhibitory (si) RNAs is a promising field of investigation. Here, we present the effective in vivo-treatment of colorectal cancer (CRC) xenograft tumors with antibody-complexed, endoribonuclease-prepared small inhibitory (esi)RNAs. We chose heterogeneous endoribonuclease-prepared siRNA pools (esiRNAs) against the frequently mutated genes PIK3CA and KRAS and coupled them to the anti-EGFR antibody cetuximab, which was internalized specifically into the tumor cells. esiRNA pools have been shown to exhibit superior specificity in target gene knockdown compared to classic siRNAs. We identified a significant decrease in tumor growth upon this treatment due to decreased tumor cell proliferation. The ex vivo-analysis of the xenograft CRC tumors revealed the expected downregulation of the intended direct targets PIK3CA and KRAS on protein level. Moreover, known downstream targets for EGFR signaling such as p-ERK, p-AKT, and c-MYC were decreased as well. We therefore propose the use of antibody-esiRNA complexes as a novel experimental treatment option against key components of the EGFR signaling cascade.
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