{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T22:28:55Z","timestamp":1790548135450,"version":"4.1.0"},"reference-count":158,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,20]],"date-time":"2020-09-20T00:00:00Z","timestamp":1600560000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Fanconi anemia (FA) is a clinically and genetically heterogeneous disorder characterized by the variable presence of congenital somatic abnormalities, bone marrow failure (BMF), and a predisposition to develop cancer. Monoallelic germline mutations in at least five genes involved in the FA pathway are associated with the development of sporadic hematological and solid malignancies. The key function of the FA pathway is to orchestrate proteins involved in the repair of interstrand cross-links (ICLs), to prevent genomic instability and replication stress. Recently, many studies have highlighted the importance of FA genes in noncanonical pathways, such as mitochondria homeostasis, inflammation, and virophagy, which act, in some cases, independently of DNA repair processes. Thus, primary defects in DNA repair mechanisms of FA patients are typically exacerbated by an impairment of other cytoprotective pathways that contribute to the multifaceted clinical phenotype of this disease. In this review, we summarize recent advances in the understanding of the pathogenesis of FA, with a focus on the cytosolic noncanonical roles of FA genes, discussing how they may contribute to cancer development, thus suggesting opportunities to envisage novel therapeutic approaches.<\/jats:p>","DOI":"10.3390\/cancers12092684","type":"journal-article","created":{"date-parts":[[2020,9,20]],"date-time":"2020-09-20T21:20:28Z","timestamp":1600636828000},"page":"2684","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Canonical and Noncanonical Roles of Fanconi Anemia Proteins: Implications in Cancer Predisposition"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2391-342X","authenticated-orcid":false,"given":"Giacomo","family":"Milletti","sequence":"first","affiliation":[{"name":"Department of Pediatric Hemato-Oncology and Cell and Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Ges\u00f9 Children\u2019s Hospital, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Strocchio","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hemato-Oncology and Cell and Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Ges\u00f9 Children\u2019s Hospital, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Pagliara","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hemato-Oncology and Cell and Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Ges\u00f9 Children\u2019s Hospital, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Girardi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hemato-Oncology and Cell and Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Ges\u00f9 Children\u2019s Hospital, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Carta","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hemato-Oncology and Cell and Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Ges\u00f9 Children\u2019s Hospital, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4408-2373","authenticated-orcid":false,"given":"Angela","family":"Mastronuzzi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hemato-Oncology and Cell and Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Ges\u00f9 Children\u2019s Hospital, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Locatelli","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hemato-Oncology and Cell and Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Ges\u00f9 Children\u2019s Hospital, 00146 Rome, Italy"},{"name":"Department of Gynecology\/Obstetrics and Pediatrics, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3039-4448","authenticated-orcid":false,"given":"Francesca","family":"Nazio","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hemato-Oncology and Cell and Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Ges\u00f9 Children\u2019s Hospital, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1002\/ajmg.a.34087","article-title":"How high are carrier frequencies of rare recessive syndromes? 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