Srividya Swaminathan, PH.D.
Título del Proyecto
Targeting the Long Isoform of the Prolactin Receptor to Prevent B-Lymphomas
Premio nombrado
Programa Familias del Congreso: Homenaje al Honorable Vic Fazio
Posición
Profesor Asistente, Biología de Sistemas
Institución
Beckman Research Institute of the City of Hope, Duarte, Calif.
Mi "por qué"
Each year, many children and adults are diagnosed with deadly forms of blood cancer of a type of immune cell known as the B cell. These cancers are particularly difficult and expensive to treat. There is an unmet clinical need in prevention and early diagnosis of B-cell malignancies, especially in people vulnerable to developing these dreadful cancers.
Mi misión
B-cell blood cancers (lymphoma and leukemia) are currently being treated with harsh chemotherapies and/or expensive immunotherapies. Despite being effective, such therapies diminish the quality of life of the patient. Prevention of B-cell malignancies using affordable strategies is key. Patients with B-cell autoimmune diseases and less aggressive forms of lymphoma are at high risk of developing aggressive, hard-to-treat, diffuse large B-cell lymphomas. We will develop an affordable and safe approach that prevents the development of this devastating type of cancer.
Descripción general de la investigación
Diffuse large B-cell lymphoma (DLBCL) is an aggressive form of blood cancer of a type of immune cell known as the B cell. Unfortunately, around 40% of people with DLBCL do not survive five years and beyond after their initial diagnosis. Safe preventative interventions for DLBCL remain an urgent clinical need. Development of such interventions requires an understanding of how DLBCLs are initiated and established at a molecular level.
During the initiation phase of DLBCL, normal B cells become pre-malignant B cells. These pre-malignant B cells then establish full-blown DLBCL. At this stage, the clinical symptoms of DLBCL become apparent. Our recent studies find that the sex hormone prolactin (PRL), which is elevated during acute and chronic stress in both males and females, initiates and establishes DLBCL. We find that PRL increases the risk of B cells transforming into deadly DLBCL in vulnerable people with autoimmune diseases and in those with milder forms of lymphoma. PRL achieves this by binding to a specific form of its receptor on B cells called the ‘long form prolactin receptor (LFPRLR)’.
Our proposed study will solidify the mechanisms by which PRL, through the LFPRLR, turns B cells malignant and ultimately establishes full-blown DLBCL.
Our findings will inform:
- Development of strategies to measure the elevation in the lymphoma-promoting LFPRLR in people at increased risk of DLBCL.
- Clinical application of safe agents that block the production of the LFPRLR, such as those used in this project, to prevent DLBCL in vulnerable populations with B cell-mediated autoimmune diseases and slow-growing B-cell lymphomas.
Por qué es importante la financiación
Because most resources are currently concentrated in treating blood cancers rather than preventing them, funds from the Prevent Cancer Foundation will allow us to advance research in blood cancer prevention. Specifically, this support will enable us to conduct essential preclinical studies that strengthen the safety and effectiveness of our proposed approach in preventing diffuse large B-cell lymphomas.
Mi esperanza
We anticipate that progress made in our study will lead to clinical trials that measure the effectiveness of our candidate agent in preventing diffuse large B-cell lymphomas in people who are at increased risk of developing this cancer.
In the long term, I hope that our affordable prophylactic approach can be used to simultaneously treat the existing B-cell disease in vulnerable people and shield them from developing diffuse large B cell lymphomas.