{
  "abstract": "The DNA damage response (DDR) is a central determinant of tumor cell fate and therapeutic response. Checkpoint kinase 1 (CHK1) and checkpoint kinase 2 (CHK2) are canonical mediators of DDR, traditionally viewed as regulators of cell-cycle arrest and genome stability. Emerging evidence reveals broader roles in coordinating cell fate decisions and tumor-immune interactions. However, how checkpoint signaling translates genotoxic stress into divergent cell fate and immune outcomes remains unresolved. Here, we synthesize current evidence to propose a graded rheostat framework in which CHK1 and CHK2 integrate genotoxic stress signals to regulate diverse cell-fate and immune outputs. Although CHK1 and CHK2 share partially overlapping functions, current evidence suggests that CHK1 often contributes to stress-adaptive buffering, whereas CHK2 is more frequently implicated in damage-associated apoptotic commitment; however, these functional tendencies vary with p53 status, tumor lineage, damage characteristics including intensity and duration, treatment context, and cellular state. These distinct yet interconnected roles may be associated with emerging non-canonical programmed cell death pathways beyond canonical apoptosis, although current evidence remains limited and context-dependent. Importantly, CHK1/CHK2 signaling also shapes the tumor immune microenvironment (TIME) by regulating cytosolic DNA accumulation, cGAS-STING activation, antigen presentation, and immune checkpoint regulation. This suggests a mechanistic interface between genomic instability and anti-tumor immunity. Together, this review provides a mechanistic and translational perspective on how DDR signaling governs cell fate and immune outcomes, thereby providing a rationale for biomarker-guided combination strategies.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China.",
    "The Second Clinical College of China Medical University, Shenyang, 110001, China.",
    "Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, 110000, China.",
    "Health Sciences Institute, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, 110122, China.",
    "The First Clinical College of China Medical University, Shenyang, 110001, China.",
    "Shenyang City University, School of Life and Health Management, 110112, China.",
    "School of Pharmacy, Queen's University Belfast, Belfast BT7 1NN, UK.",
    "Department of Cardiology, The First Hospital of China Medical University, Shenyang, 110001, China.",
    "Department of Pathology, First Hospital of China Medical University, Shenyang, 110001, China.",
    "College of Laboratory Animal Medicine of Traditional Chinese Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, China.",
    "Clinical Translational Research Center, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110002, China."
  ],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jinjia Yang"
    },
    {
      "affs": [
        1
      ],
      "name": "Zilin Liu"
    },
    {
      "affs": [
        2
      ],
      "name": "Yunzhou Chen"
    },
    {
      "affs": [
        3
      ],
      "name": "Yanling Feng"
    },
    {
      "affs": [
        4
      ],
      "name": "Yilun Liu"
    },
    {
      "affs": [
        4
      ],
      "name": "Huiyue Zheng"
    },
    {
      "affs": [
        5
      ],
      "name": "Yiran Zhao"
    },
    {
      "affs": [
        4
      ],
      "name": "Hongbo Fang"
    },
    {
      "affs": [
        6
      ],
      "name": "Yuting Chen"
    },
    {
      "affs": [
        3
      ],
      "name": "Lin Yuan"
    },
    {
      "affs": [
        3
      ],
      "name": "Ming Yang"
    },
    {
      "affs": [
        3
      ],
      "name": "Yiming Mu"
    },
    {
      "affs": [
        3
      ],
      "name": "Ning Bai"
    },
    {
      "affs": [
        7
      ],
      "name": "Ying Zhang"
    },
    {
      "affs": [
        8
      ],
      "name": "Liang Wang"
    },
    {
      "affs": [
        9
      ],
      "name": "Xiangxuan Zhao"
    },
    {
      "affs": [
        10
      ],
      "name": "Liu Cao"
    },
    {
      "affs": [
        3
      ],
      "name": "Xiaoman Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cxb1x9fpm52kg.bib",
  "cited_by": 0,
  "doi": "10.7150/ijbs.139580",
  "fulltext_url": "https://europepmc.org/articles/PMC13685761",
  "id": "cxb1x9fpm52kg",
  "issns": [
    "1449-2288"
  ],
  "landing_url": "https://europepmc.org/article/MED/42910276",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|DNA Repair Mechanisms"
    ]
  ],
  "openalex": "W7214658077",
  "pdf_url": "https://europepmc.org/articles/PMC13685761?pdf=render",
  "pmcid": "PMC13685761",
  "pmid": "42910276",
  "published": "2026-09-24",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/cxb1x9fpm52kg.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:14Z",
      "native_id": "MED:42910276",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42910276"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|DNA Repair Mechanisms",
      "subfield": "molecular-biology"
    }
  ],
  "title": "CHK1 and CHK2 as Context-Dependent Rheostats of Genotoxic Stress: Implications for Cell Fate and Tumor Immunity.",
  "title_text": "CHK1 and CHK2 as Context-Dependent Rheostats of Genotoxic Stress: Implications for Cell Fate and Tumor Immunity.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:14Z",
  "url": "https://research.draconitic.com/paper/cxb1x9fpm52kg",
  "venue": "International journal of biological sciences",
  "versions": []
}