Fanconi Anemia Pathway: Mechanisms of Breast Cancer Predisposition Development and Potential Therapeutic Targets

Abstract

The maintenance of genomic stability is crucial for species survival, and its failure is closely associated with tumorigenesis. The Fanconi anemia (FA) pathway, involving 22 identified genes, plays a central role in repairing DNA interstrand cross-links. Importantly, a germline defect in any of these genes can cause Fanconi's anemia, a heterogeneous genetic disorder, characterized by congenital growth abnormalities, bone marrow failure, and predisposition to cancer. On the other hand, the breast cancer susceptibility genes, BRCA1 and BRCA2, also known as FANCS and FANCD1, respectively, are involved in the FA pathway; hence, researchers have studied the association between the FA pathway and cancer predisposition. Here, we mainly focused on and systematically reviewed the clinical and mechanistic implications of the predisposition of individuals with abnormalities in the FA pathway to cancer, especially breast cancer.

Identification of Fanconi Anemia Pathway Genes as Novel Prognostic Biomarkers and Therapeutic Targets for Breast Cancer

“…Establishing the underlying mechanisms involved in the association between FA pathway and breast cancer, besides DNA damage repair, will have signi cant implications in clinical practice [35]. In this study, a low to high expression correlation among FA pathway genes in breast cancer was obtained, suggesting that they played a synergistic role in tumorigenesis and cancer progression.…”

The overexpression of DNA repair genes in invasive ductal and lobular breast carcinomas: Insights on individual variations and precision medicine

“…KPNA2, which encodes for Karyopherin-α2 is also highly expressed in breast cancer and its expression is associated with aggressiveness, poor outcomes in addition to chemotherapy and radiotherapy resistance [57][58][59][60][61]. The FA genes we identified as DEGs; CENPX, FAAP24, FANCD2, FANCI, UBE2T and FANCA are all overexpressed in breast cancer [62][63][64][65]. High FANCD2 expression correlated with poor breast cancer patients' outcomes.…”

Feasibility of breast radiation therapy in a Fanconi Anemia patient diagnosed with breast cancer: A case report and review of literature

“…FA patients are also known to have increased risk of breast cancer [15] , [17] , though it is not pathognomonic of FA. Recently, several FA genes including BRCA1/FANCS, BRCA2/FANCD1, PALB2/FANCN, and RAD51C/FANCO have been identified as breast carcinoma susceptibility genes [18] .…”