{
  "abstract": "RAS mutations are among the most prevalent oncogenic drivers in solid tumors and are consistently associated with suboptimal responses to radiation therapy (RT). Within this family, KRAS is the dominant isoform and a central regulator of tumor stress adaptation. Increasing evidence indicates that oncogenic KRAS orchestrates radioresistance through coordinated tumor-intrinsic and microenvironmental mechanisms. Cell-intrinsically, KRAS enhances DNA damage repair, replication stress tolerance, redox buffering, and ferroptosis defense. The KRAS–NRF2–53BP1 axis exemplifies this program by accelerating non-homologous end joining and enabling rapid repair of radiation-induced DNA double-strand breaks. Concurrently, KRAS reshapes the tumor microenvironment by promoting myeloid recruitment, metabolic rewiring, impaired antigen presentation, and immune checkpoint upregulation, thereby constraining the immunogenic effects of RT. The rapid evolution of RAS-directed therapeutics, including allele-specific, ON-state, dual-state, and pan-RAS inhibitors, as well as emerging degraders and molecular reprogramming strategies, has transformed a historically “undruggable” target into a clinically actionable vulnerability. Preclinical evidence indicates that KRAS inhibition can restore radiosensitivity and partially recondition antitumor immunity. However, adaptive resistance frequently converges on MAPK pathway reactivation and persistent immune suppression. Integrating next-generation RAS inhibitors with RT and immune-directed therapies may therefore represent a critical strategy for achieving durable tumor control in KRAS-mutant cancers.",
  "authors": [
    {
      "affiliations": [
        "Inserm U1355, Radiothérapie moléculaire et innovations thérapeutiques (RAMO-IT), Gustave Roussy, Université Paris-Saclay, Villejuif, France"
      ],
      "name": "Clément Quevrin"
    },
    {
      "affiliations": [
        "Inserm U1355, Radiothérapie moléculaire et innovations thérapeutiques (RAMO-IT), Gustave Roussy, Université Paris-Saclay, Villejuif, France"
      ],
      "name": "Michele Mondini"
    },
    {
      "affiliations": [
        "Inserm U1355, Radiothérapie moléculaire et innovations thérapeutiques (RAMO-IT), Gustave Roussy, Université Paris-Saclay, Villejuif, France"
      ],
      "name": "Lydia Meziani"
    },
    {
      "affiliations": [
        "Inserm U1355, Radiothérapie moléculaire et innovations thérapeutiques (RAMO-IT), Gustave Roussy, Université Paris-Saclay, Villejuif, France"
      ],
      "name": "Marine Gerbe-De-Thore"
    },
    {
      "affiliations": [
        "Inserm U1355, Radiothérapie moléculaire et innovations thérapeutiques (RAMO-IT), Gustave Roussy, Université Paris-Saclay, Villejuif, France"
      ],
      "name": "Winchygn Liu"
    },
    {
      "affiliations": [
        "Inserm U1355, Radiothérapie moléculaire et innovations thérapeutiques (RAMO-IT), Gustave Roussy, Université Paris-Saclay, Villejuif, France"
      ],
      "name": "Eloise Lopes"
    },
    {
      "affiliations": [
        "Inserm U1355, Radiothérapie moléculaire et innovations thérapeutiques (RAMO-IT), Gustave Roussy, Université Paris-Saclay, Villejuif, France"
      ],
      "name": "Daphné Morel"
    },
    {
      "affiliations": [
        "Inserm U1355, Radiothérapie moléculaire et innovations thérapeutiques (RAMO-IT), Gustave Roussy, Université Paris-Saclay, Villejuif, France"
      ],
      "name": "Céline Clémenson"
    },
    {
      "affiliations": [
        "Inserm U1355, Radiothérapie moléculaire et innovations thérapeutiques (RAMO-IT), Gustave Roussy, Université Paris-Saclay, Villejuif, France",
        "Department of Radiation Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France",
        "Faculté de Médecine, Université Paris Saclay, Le Kremlin-Bicêtre, France"
      ],
      "name": "Eric Deutsch"
    },
    {
      "affiliations": [
        "Inserm U1355, Radiothérapie moléculaire et innovations thérapeutiques (RAMO-IT), Gustave Roussy, Université Paris-Saclay, Villejuif, France",
        "Department of Radiation Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France",
        "Faculté de Médecine, Université Paris Saclay, Le Kremlin-Bicêtre, France"
      ],
      "name": "Antonin Levy"
    }
  ],
  "title": "RAS signaling at the crossroads of radioresistance and tumor immunity",
  "uid": "509f8fc9-ff0d-5a2d-8291-f6cc9ec0cb06"
}