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Updated: Jun 2, 2026

Engineering Oncogenic Heterozygous Gain-of-Function Mutations in Human Hematopoietic Stem and Progenitor Cells
Published on: March 10, 2023
Fanconi anaemia: from a monogenic disease to sporadic cancer
Antonio Valeri1, Sandra Martínez, José A Casado
1Hematopoiesis and Gene Therapy Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) y Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
Abstract:
The dissection of the molecular pathways participating in genetic instability disorders has rendered invaluable information about the mechanisms of cancer pathogenesis and progression, and is offering a unique opportunity to establish targeted anticancer therapies. Fanconi anaemia (FA) is a paradigm of cancer-prone inherited monogenic disorders. Moreover, accumulated evidence indicates that genetic and epigenetic alterations in FA genes can also play an important role in sporadic cancer in the general population. Here, we summarise current progress in the understanding of the molecular biology of FA and review the principal mechanisms accounting for a disrupted FA pathway in sporadic cancer. Additionally, we discuss the impact of these findings in the development of new anticancer therapies, particularly with DNA interstrand crosslinkers and with new inhibitors of the FA and/or alternative DNA repair pathways.
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