Development of Tumor Stroma-Directed Therapies
Abstract
Rationale and Objective Aims: Since the late 1800s, it was postulated the tumor cells need to exist in a proper environment in order to grow and eventually metastasize. This "soil and seed" hypothesis with the seed being the tumor cell and the soil the surrounding tissue still has merit today. While many therapies target the tumor cell, it is increasingly being recognized that therapies that treat the soil (or tumor stroma) may be necessary for successful breast cancer therapies. This project will develop an innovative model to identify early the changes in the connective tissue/tumor supporting cells (the soil) that surround the breast cancer cells. We also identified a key component of the "soil," named aortic carboxypeptidase-like protein (ACLP) that we postulate is responsible for driving breast cancer progression. These studies will provide a new strategy and approach to develop therapies that target proteins that are derived from these tumor-supporting cells and their "soil." Overarching Challenge: This project will address the overarching challenge of "what drives breast cancer growth; determine how to stop it." We will develop a novel model that examines the changes in the cells surrounding the breast cancer lesion, which will yield novel insight into breast tumor progression mechanisms. Second, we will target a breast cancer causing secreted protein, which we expect will lead to a new strategy to stop breast cancer progression. What Types of Patients Will It Help and How: Ultimately this research will benefit patients who have breast tumors that acquire resistance to current therapies. It is recognized that targeting multiple pathways will likely be needed for cures. Since we have identified a completely novel protein that changes the breast cancer cell, it is secreted, and eventually could be targeted by therapeutic antibodies it may lead to a new class of therapies. Clinical Implications, Benefits Risks: The clinical implications of this work are significant and will develop a new model to define the processes in the tumor "soil" that drive breast cancer progression. Our studies will establish the safety and efficacy of targeting specific "soil" derived proteins, which will ultimately provide benefit to women with breast cancer. These studies have no risk to patients. Projected Time to Achieve Patient-Related Outcomes: This 3-year project will develop a new model and identify the mechanism of a pro-cancerous molecule, which drives cellular changes in breast cancer. Based on these findings, phase 2 would involve generating inhibitors of ACLP and additional preclinical testing. If successful, these reagents could then be tested in women suffering from drug-resistant or aggressive tumors. Likely Impact in Ending Breast Cancer: While it is currently unknown if anything can "end breast cancer" a significant goal is to reduce disease progression. Our findings will support the concept that inhibiting molecules in the tissue in which the tumor cells are embedded and that drive cancer will result in longer survival and reduced morbidity. Our preliminary results strongly support the finding that women with high levels of ACLP have a significantly worse prognosis and if we can shift these levels (or activity) to lower amounts, we anticipate a reduced tumor burden and improved survival.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510014
Entities
People
- Matthew Layne
Organizations
- Boston University Medical Campus
- United States Army