The 5th annual Joel Walker Cancer Series meeting focused on developing strategies for best practices for precision therapy and creating the infrastructure for a molecular tumor board for FA cancer.

To provide the most effective care for people with FA who have cancer, we need to ensure that therapeutic choices are non-toxic and match each person’s unique tumor characteristics (precision therapy). A group of experts who come together to evaluate the molecular characterization of the tumors (DNA sequencing) for precision therapy, called a molecular tumor board, evaluates patients from both a clinical and molecular perspective to make accurate treatment recommendations.

In this meeting, we discussed how our understanding of the molecular pathways that regulate FA tumors can be combined with current efforts to develop a molecular tumor board for patients diagnosed with FA cancer. The meeting hosted 35 participants, including clinicians, scientists, FARF staff, and individuals with FA and their families.

Drs. Agata Smorgorzewska (Rockefeller University), Gary Kupfer (Georgetown University), Kenneth Weinberg (Stanford University), Frank Ondrey (University of Minnesota), and Daniel Johnson (University of California San Francisco) discussed recent results from their FARF-funded molecular studies that identified the FA-tumor specific changes that could be potential targets for therapy. They also discussed development of pre-clinical models, such as cell lines and animal models, that can be used to test new treatment modalities for efficacy and toxicity.

Collectively, the results from these FARF-funded researchers show that FA tumors are complex and have specific changes that could be targeted with drugs that are already being used to treat cancers in people who do not have FA. These drugs include those that target cell surface receptors or alter the growth capabilities of cancer cells without harming normal cells.

In addition to talks on the molecular studies, presentations on the current FARF and FA Europe tumor board programs and an upcoming natural history study for FA cancer were provided by Andrea Ronan (FARF Clinical Science Program Manager), Bob Dalgiesh (FA Europe), Dr. Neelam Giri (National Cancer Institute), respectively, as well as a special guest from the company, Foundation Medicine, Dr. Mehlika Hazar-Rethinam. The talks provided an overview of current efforts in place for FA tumor boards and outlined the steps needed to implement infrastructure need to host a molecular tumor board for people with FA.

Outcomes from the JW Cancer Series 5th annual meeting established that FARF will continue to advance and support molecular studies on FA tumors so that we can develop a deeper understanding of FA head and neck cancers. In tandem to that, we will implement the necessary processes for molecular characterization of FA tumors into FARF virtual tumor board evaluations to provide people with FA precision medicine-based recommendations for treatment.

Individuals with FA have an extraordinarily high lifetime risk of developing squamous cell cancers of oral mucosa, and of the epithelial lining of the proximal esophagus, vulva and anus. The origin(s) and natural history of these cancers is not yet understood. Novel preventions and better therapies are desperately needed, and surgery remains the only safe curative option.

In order to address this challenge, FARF hosted a virtual FA Cancer Ideas Lab in Fall 2021 with the generous support of the Joel Walker family.

The goal of the FA Cancer Ideas Lab was to bring scientists from all areas of expertise together to brainstorm out-of-the-box ideas that have the power to shift the paradigm of how we currently approach FA cancer. The Ideas Lab offered scientists a chance to form interdisciplinary and highly collaborative teams pitched their ideas to win $500,000 in grant funding from FARF.

The project that won is entitled Modeling the Role of Environmental Responses in Fanconi Anemia Epithelial Stem and Progenitor Cells in FA Squamous Cell Carcinoma. This grant will develop models to better understand squamous cell carcinoma in individuals with FA using non-primate animal models and organoids created from FA patient cells. These models will allow the research team to develop a deeper understanding of the influences of external environmental factors and internal elements that contribute to the onset and progression of FA cancer. The models will also be used to test cancer prevention modalities that target aldehyde or retinoid metabolism and immune factors.

The research team is comprised of Ken Weinberg and Daria Mochly-Rosen from Stanford University, Hiro Nakagawa from Columbia University, Frank Ondrey from University of Minnesota, and Craig Elmets from University of Alabama at Birmingham. Markus Grompe from Oregon Health and Science University serves as a collaborator.

The third Joel Walker Meeting took place April 23, 2020. Forty researchers, doctors, FA family members and FCF staff members joined a webinar to talk about head and neck cancer in Fanconi anemia. They sat in their home offices, second bedrooms, and living rooms to spend the day sharing their research, throwing out ideas, and piecing together a roadmap to detect, treat and prevent head and neck cancer in those with FA. Building on the framework established at previous meetings, the group included head and neck cancer experts newer to the FA community.
This year, clinicians and researchers focused largely on the following:

How to involve more individuals, via the FA Adult Council in potential studies, including clinical trials;
How to expand on screening procedures so that potential tumors are identified at an early stage;
How to develop the spectrum of opportunities, including pre-clinical models and drugs in development to identify preventive and therapeutic compounds.
FCF will continue working with this focused group (including members of the FA Adult Council and FCF Scientific Advisory Board) to expedite ways to prevent, detect, and treat HNSCC. Next steps include:

Empower the FA Adult Council to expand awareness of FA-associated HNSCC and promote the FA clinical registry;
Form a collaborative consortium that includes several academic hospitals and key researchers in the US to further evaluate how to best diagnose HNSCC at
a very early stage;
Continue to determine effective treatment and preventative strategies for FA HNSCC outside of the annual meetings.

2019

Connecting Cancer Experts

The second Joel Walker Meeting occurred April 18, 2019 in San Francisco. The aim of this day-long summit was to again bring the experts in the head and neck cancer field together to cross-pollinate ideas and build a strategy to combat HNSCC in FA patients. The program covered a wide range of topics, including treatment, early diagnosis, and emerging trends in managing head and neck cancers. The two overarching outcomes of the summit that FCF has now implemented included: (1) the development of a virtual tumor board to inform treatment; and (2) the establishment of a tissue sample system to identify effective therapies.
The virtual tumor board (VTB) is a group of medical care specialists who meet through a virtual platform to discuss individual cancer cases and determine the best possible treatment plan for the patient. A concern of the FA population is the lack of doctors experienced with adults with FA. The VTB will help address this issue.
While the virtual tumor board provides a platform to advise potential treatments, we also need a process to collect tissue samples from individuals with FA who have surgery. The bottleneck in this process has not been patient willingness or finding researchers and labs to store and analyze the samples. Instead, it has been getting the tissue from the operating room to the lab. FCF is working with a nonprofit organization that was created to enable cancer patients to direct their tumor tissue to researchers working on building cancer models. Once the patient has notified them of an upcoming surgery, FCF, along with this organization, will work directly with the hospital to obtain the tissue and transfer it to a lab. We continue to explore what a partnership with this organization will look like and feel optimistic it may provide a solution to this challenge.
These initiatives are possible thanks to the generosity of donors who give to the Joel Walker Scientific Meeting Series.

The first meeting, Head and Neck Cancer in FA: Developing Guidelines to Maximize Therapeutic Outcomes, took place in April 2018 ​at the University of Pittsburgh Medical Center.