To advance treatments and find a cure for FA, we must think big, set bold goals, and fund the best research. Since FARF was established in 1989, we have awarded 254 grants totaling $26,246,205. Donors have seen their gifts multiply in that pilot grants from FARF have enabled many FA researchers to go on to receive major grants for FA research from the National Institutes of Health and other funding sources worldwide.
Donations have helped us advance FA science more rapidly than ever thought possible. For example, no FA genes had been identified in 1989. Today, 23 genes have been discovered. Bone marrow transplant success rates for FA patients with a matched unrelated donor have risen from 0% in 1989 to over 87% today in some transplant centers that specialize in Fanconi anemia. Matched sibling donor transplants have risen from a 35% success rate to close to 100% today in those centers.
The research we fund fits into four general categories: FA solid tumors, bone marrow failure and hematopoietic malignancies, FA genes and the FA DNA repair pathway, and body systems.
Individuals with Fanconi anemia have an extremely high risk of developing squamous cell cancer in the head and neck and anogenital regions and some risk of cancers in other regions as well. The cancers that develop in FA individuals often occur at a much earlier age than what is observed in the general population and are difficult to treat due to the toxic effects of chemotherapy and radiation observed in this population. FARF supports grants that focus on defining the pathogenesis of FA solid tumors and that seek novel strategies for early detection, prevention, and treatment of these cancers.
To date, hematopoietic cell transplant (HCT) is the only curative treatment option for bone marrow failure for persons with FA. Advancements in HCT protocols and long-term care continue to improve survival rates of persons with FA following HCT. Despite these advancements, the high risk of developing squamous cell carcinoma (SCC) in individuals who have undergone an HCT is a major concern. The development of HCT-related graft-versus-host disease is correlated with increased risk; however, it is unclear whether additional factors associated with the HCT process also confer an increased risk. It is thought that the use of genotoxic chemotherapy and radiotherapy regimens may contribute to increased risk, but more studies are needed to delineate the specifics of each contributing factor. In individuals who have not yet had a transplant, the risk of progression to myelodysplastic syndrome and acute myeloid leukemia is also high. Therefore, further research is needed to develop treatments for bone marrow failure that do not rely on toxic therapies and to understand, prevent and stop the progression to hematopoietic malignancies.
Discovery of the genes that cause Fanconi anemia (FA) and the role of FA proteins in regulating DNA repair have been active areas of research over the last 30 years. Researchers have now identified 23 genes that, when mutated, cause FA, including FANCA, FANCB, FANCC, FANCD1/BRCA2, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ/BRIP1, FANCL, FANCM, FANCN/PALB2, FANCO/RAD51C, FANCP/SLX4, FANCQ/ERCC4, FANCR/RAD51, FANCS/BRCA1, FANCT/UBE2T, FANCU/XRCC2, FANCV/REV7, FANCW/RFWD3, and FANCY/FAP100. The FA proteins participate in a coordinated set of events that lead to the repair of interstrand crosslinks (ICLs) when the FA DNA repair pathway is activated during DNA replication. Variants in the FA genes cause faulty ICLrepair.
Understanding the role of specific FA variants is a critical component for identifying the potential risks and understanding the clinical course of FA patients. FARF supports grants focused on understanding the basic biology of FA genes and the DNA repair pathway to better understand how we can exploit the pathway for prevention or therapeutic purposes.
Fanconi anemia may affect multiple systems of the body. People with FA may experience endocrine disorders, arm and hand abnormalities, gynecological and/or dermatological issues, infertility, Fanconi anemia-associated neurological syndrome, mental health problems, and hearing and/or nutrition difficulties in addition to bone marrow failure and cancer. FARF supports grants focused on understanding the role of FA genes in whole body manifestations of the disease in order to improve quality of life and address the myriad of issues individuals with FA face.
We believe that research is the answer to one day making Fanconi anemia a treatable condition so that those diagnosed with the disease can live long, healthy lives. After years dedicated to gene identification, improving bone marrow transplantation, and uncovering connections to breast and other cancers, FA scientists are now poised to create less toxic therapies and improve and extend lives. Read about our funded research.