Abstract
Fanconi Anemia (FA) is a rare disorder with incidence of 1in 350,000 births. It is characterized by progressive bone marrow failure leading to death of many patients in their childhood while development of cancer at later stages of life in some. The treatment of FA is still a medical challenge. Current treatments of FA include androgen administration, hematopoietic growth factors administration and hematopoietic stem cell transplantation (HSCT). Clinical gene therapy trials are still ongoing. The partial success of current therapies has renewed interest in the search for new treatments. Generation of patient-specific induced pluripotent stem (iPS) has shown promising results for cell and gene based therapy. Small molecule interventions have been observed to delay tumor onset in FA. Tumors deficient in FA pathway can be treated by profiling of DNA repair pathway through synthetic lethality mechanism. Targeting toll-like receptor 8 (TLR8) dependent TNFα overexpression is yet another upcoming therapeutic approach to treat FA patients. In conclusion, in the present scenario of treatments available for FA, a proper algorithm of treatment decisions must be followed for better management of FA patients and to ensure their increased survival. Innovative therapeutic approaches that can prevent both anemia and cancer should be developed for more effective treatment of FA.Electronic supplementary materialThe online version of this article (doi:10.1186/1877-6566-6-1) contains supplementary material, which is available to authorized users.
Highlights
Fanconi anemia (FA) is an autosomal recessive disorder (OMIM 227650). It is characterized by bone marrow failure, developmental delay, physical abnormalities such as short stature; microcephaly; abnormal skin pigmentation; malformations of skeletal system, limbs, eyes, ears, kidneys and urinary tract, heart, genitalia, gastrointestinal system and central nervous system; and increased incidence of solid tumors and leukemias (Auerbach et al 2001; D’Andrea and Grompe 1997)
Around 14 genes are responsible for known complementation FA groups: A, B, C, D1 [BRCA2], D2, E, F, G, I, J [BRIP1], L, M, N [PALB2] and P [SLX4] are known
This could possibly explain some of the diverse cellular defects such as cell cycle defects, aberrant induction of apoptosis, and clinical heterogeneity reported in FA
Summary
Fanconi anemia (FA) is an autosomal recessive disorder (OMIM 227650). It is characterized by bone marrow failure (aplastic anemia), developmental delay, physical abnormalities such as short stature; microcephaly; abnormal skin pigmentation; malformations of skeletal system, limbs, eyes, ears, kidneys and urinary tract, heart, genitalia, gastrointestinal system and central nervous system; and increased incidence of solid tumors and leukemias (Auerbach et al 2001; D’Andrea and Grompe 1997). Interactions with these proteins suggest the diverse role of FA proteins in a number of cellular processes, such as DNA synthesis, cell cycle progression, gene expression, signal transduction, cell growth and differentiation, and protection against oxidative DNA damage. This could possibly explain some of the diverse cellular defects such as cell cycle defects, aberrant induction of apoptosis, and clinical heterogeneity reported in FA. Small molecule intervention, controlling TNFa overproduction and profiling of DNA damage repair pathway are the new emerging therapies under investigation. This review highlights the current treatments available for FA and discusses new and emerging therapeutic strategies that can be exploited for the treatment of FA in future
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