The 2014 discovery that nearly all FLC tumors share the unique DNAJ-PKAc fusion protein positioned FLC as a distinct disease driven by a unique molecular mechanism. Translation of that knowledge into new and effective patient therapies now seems achievable.
To accelerate progress towards a cure, the Foundation, working with its Medical & Scientific Advisory Board and other researchers, has identified the following priority areas for funding:
Model systems, including cell lines and genetically engineered organisms, are vital to biomedical research. While studying cancer in humans is extremely important, model systems allow scientists to make biological discoveries and test potential therapeutics in a pre-clinical setting, bridging the gap between clinician scientists and basic researchers.
Within the last decade, tremendous progress has been made in developing the first model systems for FLC. However, developing additional models, improving existing ones and making them accessible to the entire research community are critically important to sustain that progress. The growth of the FLC BioBank can provide a valuable source of tumor material for patient-derived model development efforts.
Additionally, new diagnostic tools, such as detection of the DNAJB1-PRKACA fusion in circulating tumor DNA, should also be sought in order to enable earlier identification of patients with FLC, better tracking of responses to therapy, and better assessment of the level of patients’ residual disease.
Improved epidemiological data for FLC is also needed. Published estimates of the incidence of FLC vary by more than an order of magnitude, affecting the perception of the feasibility of clinical trials, the financial support for research, and industry investment in the development of therapeutics.
The discovery of the DNAJB1-PRKACA fusion was an important milestone in our understanding of the disease. However, further research is needed to develop successful new therapeutics for FLC.
While targeting unique features of FLC, such as the chimeric DNAJB1-PKACA oncoprotein, is an important objective, understanding how DNAJB1-PRKACA leads to FLC, and determining how other molecular pathways are dysregulated in the disease are also extremely important. In addition, studies advancing our understanding of FLC cell biology and metabolism, as well as the factors that contribute to metastasis and heterogeneity within tumors and among patients remain essential.
Harnessing the immune system to treat cancer has revolutionized cancer treatment in recent years. Despite FLC’s relatively low tumor mutational burden, immunotherapy of FLC appears feasible.
Most current immunotherapies function in one of two ways:
- by removing the “brakes” of the immune system (e.g., immune checkpoint inhibitors), or
- by modifying and enhancing immune cells (e.g. CAR T-cells) to more effectively target tumors.
In addition, many other immunotherapy approaches, including cancer vaccines and tumor-targeting viruses, are currently being developed and studied for clinical use.
In order to develop effective immunotherapy approaches for FLC, research to understand the interactions between FLC tumors and the immune system, the details of the tumor microenvironment, as well as specific immune checkpoint markers for FLC will be critically important. In addition, the identification of unique cell surface markers of FLC could potentially provide a basis to develop therapeutic monoclonal antibodies and antibody-drug conjugates, or CAR T-cell therapy.
Currently, there are few effective treatments for FLC aside from surgical resection and no clinically-proven systemic therapies to manage advanced disease. Since a significant number of FLC patients have metastatic disease at the time of diagnosis, new therapeutics are urgently needed for FLC.
The Foundation is committed to supporting the development of the clinical trials necessary to bring new therapies to FLC patients and support the development of an evidence-based standard of care for the disease.