The Latest on FA Research

Research is the answer to one day making FA a treatable, manageable disease.

Here, you’ll discover the most recent strides in FA research and activities funded by FCF. Every quarter, we’ll bring you updates on newly funded grants, ongoing projects, and significant milestones.

None of this progress would be possible without the unwavering support of our generous donors, fundraisers, and passionate researchers. Join us in fueling this vital research by making a gift today.

Last updated: April 30, 2024

Projects that Wrapped Up in 2024

Synthetic Lethal Approaches to Treatment of Fanconi Anemia (FA) Gene Mutant Head and Neck Cancer
Barbara Burtness, MD, and Gary Kupfer, MD
Yale University and Georgetown University
Funded in 2020

Dr. Burtness and Dr. Kupfer’s study aimed to achieve several objectives: first, they sought to pinpoint and confirm specific genetic mutations in a type of head and neck squamous cell carcinoma. Next, they aimed to create laboratory models of this cancer using samples that had the identified mutations. Finally, they tested different drugs to see if they could effectively target the vulnerabilities in these mutated cells.

Their research revealed two promising approaches for treating head and neck cancer with Fanconi gene defects. One approach involves using existing drugs, which are ready for immediate testing and could soon be used in clinical trials. The other approach focuses on developing a new drug that targets a previously unexplored biological pathway. Both strategies hold potential for improving treatment outcomes for individuals with Fanconi anemia who are at risk of developing head and neck cancer.

A Small Molecule Approach to Overcome Replication Dysfunction in FA
Sharon Cantor, PhD, and Peter Kurre, MD
University of Massachusetts Medical School and Children’s Hospital of Philadelphia
Funded in 2020

Dr. Cantor and Dr. Kurre’s study aimed to address bone marrow failure in individuals with FA by targeting the DNA replication issue underlying the condition. They developed a reliable method to assess DNA replication gaps, which are elevated in cells lacking the FA pathway. Using bone marrow from mice with specific FA gene deficiencies, they successfully expanded long-term hematopoietic stem cells (HSCs) in vitro, demonstrating their potential for transplantation. This discovery is significant because hematopoietic failure due to HSPC loss is a major cause of health problems and death in FA patients. The adapted protocol for this research is available upon request by contacting Dr. Cantor or Dr. Kurre via email. Sharon.Cantor@umassmed.edu and KURREP@chop.edu. 

Ongoing Projects

Psychosocial Experiences of Adults with Fanconi Anemia: A Participatory Mixed-Methods Research Study
Kathleen Bogart, PhD, and Megan Voss, DNP
Oregon State University and University of Minnesota
Funded in 2022

Dr. Bogart and Dr. Voss focuses on understanding mental health outcomes in individuals with FA, revealing high rates of PTSD, anxiety, and depression, alongside common challenges such as stigma and fertility issues. Their research emphasizes the importance of accessible mental health support and community connections, particularly for marginalized groups, with recommendations intended for the Fanconi Cancer Foundation.

National Institutes of Health (NIH) Center Comprehensive Program for Natural History of Development of Squamous Cell Carcinoma in Fanconi Anemia
Neelam Giri, MD, and Sharon Savage, MD
National Institutes of Health
Funded in 2022

Dr. Giri and Dr. Savage’s study aims to establish a central facility for comprehensive screening of individuals with FA, tracking cancer development through detailed evaluations and biospecimen collection. With more than 50 enrolled participants, the study collaborates with other FA investigators to uncover genetic and immunological mechanisms underlying cancer susceptibility in FA, ultimately aiding in early detection and treatment strategies for this high-risk population.

Cytology Based DNA Analysis to Investigate the Malignant Potential of Oral Lesions in Patients with Fanconi Anemia
Martial Guillaud, PhD, and Denise Laronde, PhD
BC Cancer
Funded in 2022

Dr. Guillaud and Dr. Laronde are working to create and test a semi-automatic DNA image cytometry platform to detect aneuploidy in oral cancer among individuals with FA. Utilizing deep learning algorithms and analyzing sixty oral brush biopsy specimens, their study seeks to enable early lesion identification, potentially improving survival rates for this high-risk population through timely interventions and treatments.

Oral Mucosal Gene Therapy as a Prevention for FA-Associated Cancers
Markus Grompe, MD, and Ray Monnat, MD
Oregon Health and Science University and University of Washington
Funded in 2022

Dr. Grompe and Dr. Monnat are developing advanced imaging techniques for studying mouth tissue in mice, improve methods for delivering genes into the mouth of mice with FA, and investigate whether fixing FA-related gene defects in mouth cells provides an advantage. They found that a certain type of genetic material can effectively enter mouth cells and that a specific gene plays a role in the development of mouth cancer in mice with FA. Their work could lead to better ways of detecting early mouth cancers in both mice and humans with FA, and might eventually open the door for gene therapy trials to treat FA-related mouth problems.

Modeling Environmental Responses of Fanconi Anemia Epithelial Stem and Progenitor Cells to Prevent Squamous Cell Carcinoma
Hiroshi Nakagawa, MD, PhD, and Kenneth Weinberg, MD
Colombia University and Stanford University
Funded in 2022

Dr. Nakagawa and Dr. Weinberg are working to understand how modifying certain compounds and using retinoid treatment affect the development of squamous cell carcinoma (SCC) in FA mouse models. Their research also involves studying 3D organoids to learn more about SCC biology and how it responds to treatment. By identifying potential cancer-causing mechanisms and testing drugs, their study could lead to preventive measures for cancer in individuals with FA, who are particularly vulnerable to cancer treatments.

Building Collaborative Partnerships to Understand Fanconi Anemia Tumor Pathogenesis, Prevention, and Treatment
Agata Smogorzewska, MD, PhD
The Rockefeller University
Funded in 2022

Dr. Smogorzewska’s study aims to unite stakeholders in the FA cancer consortium, expand clinical partnerships, establish a data-sharing platform, and create patient-derived models for research. They’ve identified a potential marker for pre-malignant oral lesions in FA individuals and are working to validate it further. Collaborating with various institutions, their research seeks to improve treatments for FA by involving patients, families, physicians, and researchers.

Updates on Other Research Initiatives

Data Commons Initiative (aka FRIENDS)

The FRIENDS initiative, the Fanconi Research Initiative for Education, Networking, and Data Sharing, has launched to foster collaboration in the FA community, highlighted by recent meetings to establish a data commons. Together with our partners Data for the Common Good, these efforts aim to pool global expertise and data to address various scientific priorities, including:

• Cancer
• Fertility
• Bone marrow failure
• Psychosocial research
• Breakage analysis and diagnosis
• Environmental exposures
• Developmental abnormalities
• Family history
• Demographics
• Community engagement
• Genetics
• Dietary history
• Fanconi Associated Neurological Syndrome (FANS)

Scientists, families, patients, and advocates are encouraged to contribute to this collaborative effort by contacting Laura Hefner at laura@fanconi.org.

Fanconi Anemia Neurological Syndrome (FANS)

The FANS board recently convened for the first time on March 8th, where Dr. Prashanth Ramachandran shared updates on his ongoing research supported by an FCF grant. Collaborating with Dr. MoY Fiesco-Roa and Dr. Eunike Velleuer-Carlberg, Dr. Ramachandran’s team has recruited six individuals with FANS and is developing a database to consolidate data from FANS cases worldwide, with the aim of integrating it into the FRIENDS initiative.

Charting a Path Forward for FA Cancer Prevention Trials

On Friday, April 12, more than 60 participants, including those with FA, researchers, clinicians, and family members, participated in a virtual meeting focused on planning FA cancer prevention clinical trials. The goal was to review existing data and agree on the next steps for launching a collaborative chemoprevention trial across multiple institutions.