{"entity": "researcher", "timestamp": "2026-08-20T20:26:08.643Z", "family": "Broggini", "given": "Massimo", "initials": "M", "orcid": "0000-0002-8138-9358", "affiliations": ["Laboratory of Molecular Pharmacology IRCCS-Istituto di Ricerche Farmacologiche \"Mario Negri\", Milan, Italy."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/b1e8ef5869dd4419a5c540a3071e7217.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/b1e8ef5869dd4419a5c540a3071e7217"}}, "publications": [{"entity": "publication", "iuid": "0562f7ae9ae74ce9be218b4602dcd4c7", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/0562f7ae9ae74ce9be218b4602dcd4c7.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/0562f7ae9ae74ce9be218b4602dcd4c7"}}, "title": "The integrated stress response is tumorigenic and constitutes a therapeutic liability in KRAS-driven lung cancer.", "authors": [{"family": "Ghaddar", "given": "Nour", "initials": "N"}, {"family": "Wang", "given": "Shuo", "initials": "S"}, {"family": "Woodvine", "given": "Bethany", "initials": "B", "orcid": "0000-0001-8359-6476", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5b06f2ec71304b0196962103c15aefe9.json"}}, {"family": "Krishnamoorthy", "given": "Jothilatha", "initials": "J"}, {"family": "van Hoef", "given": "Vincent", "initials": "V"}, {"family": "Darini", "given": "Cedric", "initials": "C"}, {"family": "Kazimierczak", "given": "Urszula", "initials": "U"}, {"family": "Ah-Son", "given": "Nicolas", "initials": "N"}, {"family": "Popper", "given": "Helmuth", "initials": "H", "orcid": "0000-0003-4970-1265", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5c125771dd9d40b28c0ec1108a2efdb8.json"}}, {"family": "Johnson", "given": "Myriam", "initials": "M"}, {"family": "Officer", "given": "Leah", "initials": "L", "orcid": "0000-0002-3690-2386", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9244a991003b48c4a624ff9fc105c50c.json"}}, {"family": "Teod\u00f3sio", "given": "Ana", "initials": "A", "orcid": "0000-0002-1386-6730", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f87a35d99867490aaf8e1120130837a8.json"}}, {"family": "Broggini", "given": "Massimo", "initials": "M", "orcid": "0000-0002-8138-9358", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b1e8ef5869dd4419a5c540a3071e7217.json"}}, {"family": "Mann", "given": "Koren K", "initials": "KK"}, {"family": "Hatzoglou", "given": "Maria", "initials": "M", "orcid": "0000-0003-2037-1231", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3fbc5330f8c84c548a8472bb81cf77f3.json"}}, {"family": "Topisirovic", "given": "Ivan", "initials": "I", "orcid": "0000-0002-5510-9762", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1bca1813f34c4864940ac6593044a9cc.json"}}, {"family": "Larsson", "given": "Ola", "initials": "O", "orcid": "0000-0003-1412-1308", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3f81c6cbbe564d38bc78d1af5153d804.json"}}, {"family": "Le Quesne", "given": "John", "initials": "J", "orcid": "0000-0003-3552-7446", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a6bbfa845cda4379b505dbb0091edcf6.json"}}, {"family": "Koromilas", "given": "Antonis E", "initials": "AE", "orcid": "0000-0003-1972-0799", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7825afc7ac8942819083ce7c570b5508.json"}}], "type": "journal article", "published": "2021-07-30", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "12", "issue": "1", "pages": "4651", "issn-l": "2041-1723"}, "abstract": "The integrated stress response (ISR) is an essential stress-support pathway increasingly recognized as a determinant of tumorigenesis. Here we demonstrate that ISR is pivotal in lung adenocarcinoma (LUAD) development, the most common histological type of lung cancer and a leading cause of cancer death worldwide. Increased phosphorylation of the translation initiation factor eIF2 (p-eIF2\u03b1), the focal point of ISR, is related to invasiveness, increased growth, and poor outcome in 928 LUAD patients. Dissection of ISR mechanisms in KRAS-driven lung tumorigenesis in mice demonstrated that p-eIF2\u03b1 causes the translational repression of dual specificity phosphatase 6 (DUSP6), resulting in increased phosphorylation of the extracellular signal-regulated kinase (p-ERK). Treatments with ISR inhibitors, including a memory-enhancing drug with limited toxicity, provides a suitable therapeutic option for KRAS-driven lung cancer insofar as they substantially reduce tumor growth and prolong mouse survival. Our data provide a rationale for the implementation of ISR-based regimens in LUAD treatment.", "doi": "10.1038/s41467-021-24661-0", "pmid": "34330898", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8324901"}, {"db": "pii", "key": "10.1038/s41467-021-24661-0"}], "notes": [], "created": "2026-08-20T08:51:39.836Z", "modified": "2026-08-20T08:51:40.199Z"}]}