{
  "id": 14984296,
  "title": "Lipid nanoparticle-mediated RNAi targeting of KRAS mutants sensitises colorectal cancer cells to chemotherapy",
  "url": "https://urgent.news/2026/10/16/lipid-nanoparticle-mediated-rnai-targeting-of-kras-mutants-sensitises",
  "topic": "health",
  "section": "Health & Medicine",
  "published": "2026-10-16T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.10.15.759489v1?rss=1"
  },
  "original_language": "en",
  "account": "Kelley reported on a promising new approach that targets KRAS mutations in colorectal cancer cells using lipid nanoparticles (LNP)-mediated RNA interference (RNAi). KRAS mutations, such as G12D, G12V, and G13D, are known to drive colorectal cancer (CRC) growth and contribute to therapeutic resistance. Currently, approved KRAS inhibitors only target the G12C subtype, leaving the more prevalent variants without targeted therapies.\n\nThe research team developed an LNP-based RNAi strategy that utilizes a single small interfering RNA (siRNA) sequence to silence all three KRAS variants. This approach effectively reduced KRAS mRNA and protein expression in HCT116 (G13D), SW620 (G12V), and LS180 (G12D) cells, without affecting the KRAS wild-type HT29 cells. By silencing KRAS, the researchers observed a decrease in cellular proliferation, clonogenic survival, and migration in the cancer cells.\n\nFurther investigation revealed changes in KRAS-associated signaling pathways, including suppression of cell-cycle and DNA repair programs. This provided a rationale for combining siRNA silencing with the fluoropyrimidine chemotherapeutic agent, 5-fluorouracil (5-FU). The combination treatment showed synergistic effects across all three KRAS-mutant CRC cell models, enhancing apoptosis in both monolayer cultures and 3D spheroids.\n\nThese findings offer proof of concept for the proposed combination strategy, suggesting its potential as a therapeutic approach for KRAS-mutant CRC. The researchers emphasize the need for further investigation to validate these results and explore the clinical applicability of this novel treatment strategy.",
  "summary": "KRAS mutations, including G12D, G12V and G13D, are major oncogenic drivers in colorectal cancer (CRC) and are associated with therapeutic resistance. However, approved KRAS inhibitors remain focused on G12C subtype, leaving these prevalent variants without approved targeted therapies. Here, we developed a lipid nanoparticle (LNP)-based RNA interference (RNAi) strategy to target these three KRAS…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 2,
    "also_reported_by": [
      {
        "outlet": "STAT News",
        "title": "STAT+: Verastem’s KRAS inhibitor shows promise in pancreatic cancer",
        "url": "https://urgent.news/2026/10/15/stat-verastems-kras-inhibitor-shows-promise-in-pancreatic-cancer",
        "published": "2026-10-15T15:43:15.000Z"
      }
    ]
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}