{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T21:22:06Z","timestamp":1790457726162,"version":"4.1.0"},"reference-count":51,"publisher":"American Society for Clinical Investigation","issue":"11","license":[{"start":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T00:00:00Z","timestamp":1654646400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"crossref","award":["ANR-15-CE17-0006-01"],"award-info":[{"award-number":["ANR-15-CE17-0006-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004099","name":"Ligue Nationale Contre le Cancer","doi-asserted-by":"crossref","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100004099","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,8]]},"abstract":"<jats:p>\n                    DNA damage and genomic instability contribute to non\u2013small cell lung cancer (NSCLC) etiology and progression. However, their therapeutic exploitation is disappointing. CTC-derived explants (CDX) offer systems for mechanistic investigation of CTC metastatic potency and may provide rationale for biology-driven therapeutics. Four CDX models and 3 CDX-derived cell lines were established from NSCLC CTCs and recapitulated patient tumor histology and response to platinum-based chemotherapy. CDX (GR-CDXL1, GR-CDXL2, GR-CDXL3, GR-CDXL4) demonstrated considerable mutational landscape similarity with patient tumor biopsy and\/or single CTCs. Truncal alterations in key DNA damage response (DDR) and genome integrity\u2013related genes were prevalent across models and assessed as therapeutic targets in vitro, in ovo, and in vivo. GR-CDXL1 presented homologous recombination deficiency linked to biallelic\n                    <jats:italic>BRCA2<\/jats:italic>\n                    mutation and\n                    <jats:italic>FANCA<\/jats:italic>\n                    deletion, unrepaired DNA lesions after mitosis, and olaparib sensitivity, despite resistance to chemotherapy. SLFN11 overexpression in GR-CDXL4 led to olaparib sensitivity and was in coherence with neuroendocrine marker expression in patient tumor biopsy, suggesting a predictive value of SLFN11 in NSCLC histological transformation into small cell lung cancer (SCLC). Centrosome clustering promoted targetable chromosomal instability in GR-CDXL3 cells. These CDX unravel DDR and genome integrity\u2013related defects as a central mechanism underpinning metastatic potency of CTCs and provide rationale for their therapeutic targeting in metastatic NSCLC.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.155804","type":"journal-article","created":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T12:00:55Z","timestamp":1651752055000},"source":"Crossref","is-referenced-by-count":17,"title":["Targeting genome integrity dysfunctions impedes metastatic potency in non\u2013small cell lung cancer circulating tumor cell\u2013derived explants"],"prefix":"10.1172","volume":"7","author":[{"given":"Tala","family":"Tayoun","sequence":"first","affiliation":[{"name":"Gustave Roussy, Paris-Saclay University, \u201cCirculating Tumor Cells\u201d Translational Platform, CNRS UMS3655 \u2013 INSERM US23 AMMICA, Villejuif, France."},{"name":"INSERM, U981 \u201cIdentification of Molecular Predictors and new Targets for Cancer Treatment\u201d, 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