{
  "id": 10907410,
  "title": "Lung cancers can use two different mechanisms to evade KRAS-inhibiting drugs",
  "url": "https://urgent.news/2026/09/30/lung-cancers-can-use-two-different-mechanisms-to-evade-kras",
  "topic": "health",
  "section": "Health & Medicine",
  "published": "2026-09-30T09:00:00.000Z",
  "source": {
    "name": "MIT News Research",
    "slug": "mit-news-research",
    "url": "https://news.mit.edu/2026/lung-cancers-can-use-two-different-mechanisms-evade-kras-inhibiting-drugs-0930"
  },
  "original_language": "en",
  "account": "Approximately one quarter of lung adenocarcinomas carry KRAS gene mutations that cause uncontrolled cell growth. While FDA-approved KRAS inhibitors initially show promise, tumors almost always develop resistance. This resistance typically stems from either cells reactivating KRAS activity or increasing KRAS expression, overpowering the inhibitor's effects. MIT researchers have discovered an alternative mechanism by which lung tumors can become resistant to KRAS inhibition. In some cases, lung tumors transform from adenocarcinoma to squamous cell carcinoma, a process that enables cancer cells to bypass KRAS dependency and activate alternative growth pathways. Carrying out this study, MIT graduate students Carrie Rodriguez and Nicolas Mathey-Andrews, along with their senior author Tyler Jacks, professor of biology and director of the Koch Institute for Integrative Cancer Research, have published their findings in the journal Nature Genetics. KRAS inhibitors are effective in around 35% of patients, but typically lead to resistance within these patients. To uncover the factors driving this transformation, researchers engineered a mouse lung cancer model expressing the KRAS inhibitor-targeted mutation. Subsequent treatment with a KRAS-G12C inhibitor enabled tumors with loss of the Nkx2-1 gene—responsible for maintaining alveolar epithelial identity—to transition from adenocarcinoma to squamous cell carcinoma. Additional factors contributing to this transition include overactivation of DeltaNp63 and SOX2 transcription factors, both of which are overexpressed in squamous cell carcinomas. Crucially, tumors undergoing this tissue transformation do not acquire KRAS expression-enhancing mutations seen in adenocarcinomas; instead, KRAS signaling is suppressed, allowing the cells to continue growing through alternative pathways. As the researchers further investigate these transformations, they aim to identify vulnerabilities in squamous transformation that could be targeted by new therapeutic drugs.",
  "summary": "Some tumor cells develop resistance by amplifying the KRAS gene, while others change their tumor type, MIT researchers have found.",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "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."
}