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The Fanconi anemia pathway and Breast Cancer: A comprehensive review of clinical data

Published:August 10, 2021DOI:https://doi.org/10.1016/j.clbc.2021.08.001

      Highlights

      • The FA pathway includes 22 genes involved in the repair of damaged DNA
      • Dysregulation of the FA pathway is associated with familial/sporadic breast cancer
      • Additional genes involved in breast cancer may be later classified as FA genes
      • Targeted therapies (PARPis) exploiting FA pathway gene defects have been developed

      Abstract

      The development of breast cancer depends on several risk factors, including environmental, lifestyle and genetic factors. Despite the evolution of DNA sequencing techniques and biomarker detection, the epidemiology and mechanisms of various breast cancer susceptibility genes have not been elucidated yet. Dysregulation of the DNA damage response causes genomic instability and increases the rate of mutagenesis and the risk of carcinogenesis. The Fanconi Anemia (FA) pathway is an important component of the DNA damage response and plays a critical role in the repair of DNA interstrand crosslinks and genomic stability. The FA pathway involves 22 recognized genes and specific mutations have been identified as the underlying defect in the majority of FA patients. A thorough understanding of the function and epidemiology of these genes in breast cancer is critical for the development and implementation of individualized therapies that target unique tumor profiles. Targeted therapies (PARP inhibitors) exploiting the FA pathway gene defects have been developed and have shown promising results. This narrative review summarizes the current literature on the involvement of FA genes in sporadic and familial breast cancer with a focus on clinical data derived from large cohorts.

      Keywords

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