Selection of Anti-R-Spondin Antibody for Targeting Cancer Stem Cells
Stem cell pathways have long been recognized to be aberrantly activated in cancer. These stem cell pathways play important roles in regulating self-renewal, a process by which a stem cell is able to undergo unlimited cell division. They also control differentiation, a process by which stem cells give rise to cells with specialized functions. Inappropriate activation of self-renewal and/or blockage of terminal differentiation support tumor growth and metastatic spread of disease, and are the hallmark of cancer stem cells (CSCs). Thus CSCs comprise a subset of the malignant cells, but drive cancer progression. It is now understood that current chemotherapeutics do not effectively eliminate CSCs, leading to tumor recurrence, and predictably poor prognosis. Developing a new generation of therapeutics that target CSCs, therefore represents a promising novel approach to cancer treatment. Our mission is to develop such agents. We have identified and validated a therapeutic target that belongs to a stem cell pathway, and is essential for CSC maintenance in solid tumors. We propose to generate and select an antibody that will inactivate the target in primary and metastatic tumors, leading to the elimination of CSCs and control of tumor progression. The novel therapeutic strategy described in this grant application program could lead to first-in-class therapeutics targeting a CSC pathway. A large body of pre-clinical work shows that this therapeutic strategy has tremendous potential.
This grant is to support research on a therapeutic targeting an important stem cell pathway. Knowledge and experience gained in this work will benefit our understanding not only of cancer stem cells (CSCs), but also normal stem cells. California is well positioned to lead the new medical revolution enabled by stem cell discoveries. [Redacted] has demonstrated a capacity to discover innovative new medicines with three first-in-class novel therapeutics targeting CSCs now in clinical studies for the treatment of solid tumors. This grant will help to build [redacted]’s leading position in the CSC field, and at the same time broaden our knowledge of stem cell biology. Success in this effort will benefit California both in near term jobs and in helping California remain a leader in stem cell research.