1. Figure 1 Exosomes with siRNAs targeting
the KRASG12D oncogene in experimental pancreatic cancer models
Figure 1 | Exosomes with siRNAs targeting the KRASG12D oncogene in experimental pancreatic cancer models. Purified exosomes from normal human foreskin fibroblasts are loaded with small interfering RNA (siRNA) or short hairpin RNA that silences KRASG12D (forming iExosomes) (1). iExosomes containing CD47 have limited clearance in the circulation (phagocytosis by monocytes is prevented) compared with CD47− iExosomes and iLiposomes (serving as controls) (2). Pancreatic cancer cells uptake iExosomes via macropinocytosis (3). siRNA targeting KRASG12D reduces KRAS GTPase activity and downstream activation of RAF–MEK–ERK or PI3K–AKT–mTOR signalling, inhibits cell proliferation and increases pancreatic cancer cell apoptosis (4). iExosomes injected intraperitoneally are preferentially taken up by pancreatic cancer cells, and markedly inhibit tumour growth and metastatic progression (5).
Buscail, L. (2017) Exosomes for targeting KRAS in the treatment of pancreatic cancer
Nat. Rev. Gastroenterol. Hepatol. doi: /nrgastro