Research ArticleCancer

Targeting KRAS-dependent tumors with AZD4785, a high-affinity therapeutic antisense oligonucleotide inhibitor of KRAS

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Science Translational Medicine  14 Jun 2017:
Vol. 9, Issue 394, eaal5253
DOI: 10.1126/scitranslmed.aal5253

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An antisensible approach to targeting KRAS

Mutations that cause activation of the KRAS oncogene are common in human cancer, including treatment-resistant tumor types such as lung and pancreatic cancer. KRAS has also proven to be notoriously difficult to target with small molecules. To overcome this issue, Ross et al. have turned to genetic technology, demonstrating an antisense oligonucleotide–based therapy for inhibiting KRAS. The antisense oligonucleotide used in this study was chemically modified, allowing systemic delivery through subcutaneous injection and avoiding the need for a specialized delivery vehicle. The authors tested the efficacy of this therapy in multiple mouse models of non–small cell lung cancer and evaluated its safety in primates, demonstrating its potential suitability for translation to humans.

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