Final Report Summary - TUMORGAN (Exploring the tumor as a communicating organ)
A tumor is comprised of multiple cell types that collectively evolve into a clinically manifested and deadly disease through continuous interplay between malignant cells and their microenvironment. Our studies explore the full complexity of cell types comprising the vasculature and connective tissue of tumors in order to detail their usefulness as cancer drug targets or markers of the severity of the disease. Fulfillment of the aims of our studies is made possible through a series of methodological refinements. Firstly, we aim to unravel the full complexity of different cell types residing within tumors by ascribing functional roles to subgroups of cells through the use of technology enabling massive parallel analysis of single cells. Secondly, we investigate novel strategies for therapeutic targeting of cancer. Thirdly, using exclusive patient materials, we investigate the prognostic significance of the different subsets of cells residing in the tumor microenvironment.
The project upon completion has achieved the following outcomes: 1) We have delineated a novel role for the tumor microenvironment as a determinant of breast cancer prognosis, metastasis and treatment response. The studies have identified a new point of intervention between cancer cells and the surrounding connective tissue, leading to conversion of the most aggressive form of the disease into a comparatively more indolent tumor, which is amenable for treatment with conventional hormone-blocking therapies known to be efficacious. 2) We have explored a role for the blood vessel wall as a barrier for dissemination of tumor cells into distant locations. Metastatic diffusion is the cause of >90% of cancer-related deaths. By in depth studies of the tumor vasculature, we have identified optimal targets for therapeutic targeting with the aim to reduce metastatic spread.
Taken together, our integrated approach combining high resolution studies of basic biology with the use of disease-specific models of cancer and exclusive patient materials has proven successful in uncovering new information that is immediately useful for the management of malignant diseases.
The project upon completion has achieved the following outcomes: 1) We have delineated a novel role for the tumor microenvironment as a determinant of breast cancer prognosis, metastasis and treatment response. The studies have identified a new point of intervention between cancer cells and the surrounding connective tissue, leading to conversion of the most aggressive form of the disease into a comparatively more indolent tumor, which is amenable for treatment with conventional hormone-blocking therapies known to be efficacious. 2) We have explored a role for the blood vessel wall as a barrier for dissemination of tumor cells into distant locations. Metastatic diffusion is the cause of >90% of cancer-related deaths. By in depth studies of the tumor vasculature, we have identified optimal targets for therapeutic targeting with the aim to reduce metastatic spread.
Taken together, our integrated approach combining high resolution studies of basic biology with the use of disease-specific models of cancer and exclusive patient materials has proven successful in uncovering new information that is immediately useful for the management of malignant diseases.