EFTX-G12V: a novel KRASG12V-selective RNAi therapeutic

Kostas A Papavassiliou; Alice G Vassiliou; Athanasios G Papavassiliou

doi:10.1016/j.tips.2025.07.004

EFTX-G12V: a novel KRAS^G12V-selective RNAi therapeutic

Trends Pharmacol Sci. 2025 Sep;46(9):820-822. doi: 10.1016/j.tips.2025.07.004. Epub 2025 Jul 25.

Authors

Kostas A Papavassiliou¹, Alice G Vassiliou², Athanasios G Papavassiliou³

Affiliations

¹ First University Department of Respiratory Medicine, 'Sotiria' Chest Hospital, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece.
² First Department of Critical Care Medicine, 'Evangelismos' Hospital, Medical School, National and Kapodistrian University of Athens, Athens 10676, Greece.
³ Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece. Electronic address: papavas@med.uoa.gr.

PMID: 40713293
DOI: 10.1016/j.tips.2025.07.004

Abstract

KRAS^G12V-driven cancers remain therapeutically elusive. Recently, Stanland and colleagues developed EFTX-G12V, a GE11-conjugated small interfering RNA (siRNA) that selectively silences KRAS^G12V and achieves tumor regression by inhibiting oncogenic signaling and angiogenesis and enhancing anti-tumor immunity. EFTX-G12V represents an innovative RNAi-based precision oncology strategy for previously undruggable oncogenic mutations.

Keywords: EFTX-G12V; KRAS(G12V); RNAi; antitumor immune response; oncogenic signaling.

MeSH terms

Animals
Humans
Mutation
Neoplasms* / genetics
Neoplasms* / therapy
Proto-Oncogene Proteins p21(ras)* / genetics
RNA Interference
RNA, Small Interfering* / administration & dosage
RNA, Small Interfering* / genetics
RNAi Therapeutics* / methods

Substances

Proto-Oncogene Proteins p21(ras)
RNA, Small Interfering
KRAS protein, human