{
  "id": 17613153,
  "title": "Homoharringtonine targets XPC to inhibit DNA damage repair and sensitize tumors to platinum-based chemotherapy",
  "url": "https://urgent.news/2026/11/01/homoharringtonine-targets-xpc-to-inhibit-dna-damage-repair-and",
  "topic": "health",
  "section": "Health & Medicine",
  "published": "2026-11-01T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762176v1?rss=1"
  },
  "original_language": "en",
  "account": "DNA damage repair (DDR) is critical for maintaining genomic stability and serves as a promising target for cancer therapy development. Researchers have discovered that homoharringtonine (HHT), a drug previously used to treat leukemia, can inhibit DDR, offering a new way to boost the effectiveness of platinum-based chemotherapy.\n\nUsing a high-content screening method, scientists identified HHT as a novel DDR inhibitor. This drug binds tightly to XPC, a vital component of nucleotide excision repair (NER) that repairs damaged DNA. Specifically, HHT attaches to Thr795 of XPC with high affinity (Kd = 158.4 nM). By interfering with XPC's interaction with damaged DNA, HHT disrupts NER and decreases the efficiency of non-homologous end joining (NHEJ), a second DNA repair pathway.\n\nAs a result, HHT makes tumor cells more susceptible to platinum-based chemotherapy both in laboratory tests and animal models. This discovery demonstrates that a phenotype-driven screening approach can efficiently uncover potential DDR inhibitors. Furthermore, HHT emerges as a unique XPC inhibitor, opening up new possibilities for enhancing the effectiveness of platinum-based therapies in solid tumors.",
  "summary": "DNA damage repair (DDR) is essential for preserving genomic stability and also represents a key targetable axis in cancer drug development. Here, we identify and validate homoharringtonine (HHT), a clinically approved antileukemic drug, as a novel DDR inhibitor using a phenotype-driven, high-content screen based on 53BP1 Tudor-domain foci formation. Mechanistically, HHT directly binds XPC, a…",
  "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."
}