Main Content

Tumor-stroma crosstalk in cancer

The tumor microenvironment is increasingly recognized as an essential component of tumorigenesis. The crosstalk between cancer cells and stromal cells results in tumor progression and often determines therapeutic response. The tumor stroma includes cellular components such as immune cells, fibroblasts, endothelium, extracellular matrix and soluble factors. Our research focuses on developing new translatable approaches to target different stromal/immune cell populations and their corresponding signaling systems with an aim to suggest novel therapeutic strategies to treat cancer. Specifically, we study the pathological role of fibroblasts, macrophages and their link to immune response, mainly in lung and pancreatic cancer. p38MAPK pathway is one of the key regulators of stroma-mediated tumorigenesis, involved in secretion of soluble factors and matrix components to support cancer progression. We are interested in understanding the mechanisms how p38MAPK controls the functions of stromal cells aiming to identify novel druggable targets in the pathway. We look for potential biomarkers and anti-cancer targets that are secreted by the tumor stroma and could be detected in blood plasma of the patients. We employ also an encapsulation methodology to deliver bioactive molecules into tumor-associated macrophages to enhance the efficacy of lung cancer therapy. To achieve the goals, we combine basic research with translational aspects analyzing liquid and tumor tissue biopsies and use mouse models of cancer.

Literature:

Novoselova M§, Loh HM§, Trushina D, Ketkar A, Abakumova T, Zatsepin T, Kakran M, Brzozowska A, Hong LH, Gorin D, Antipina M*, Brichkina A*. Biodegradable Polymeric Multilayer    Capsules for Therapy of Lung Cancer. ACS Applied Materials and Interfaces 12, 5610-5623, 2020
Brichkina A and Bulavin DV. Cancer suppression by systemic inactivation of p38MAPK. Oncotarget Feb 11. doi: 10.18632/oncotarget.15293, 2017
Brichkina A, Bertero T, Loh HM, Nguyen NTM, Emelyanov A, Rigade S, Ilie M, Hofman P, Gaggioli C, Bulavin DV. p38MAPK builds a hyaluronan cancer niche to drive lung tumorigenesis. Genes Dev 30, 2623–2636, 2016
Brichkina A, Nguyen NT, Baskar R, Wee S, Gunaratne J, Robinson RC, Bulavin DV. Proline isomerisation as a novel regulatory mechanism for p38MAPK activation and functions. Cell Death Differ 23, 1592-601, 2016.

Funding:

DFG BR 5849/1-1, KFO325 start-up, UKGM, Novartis-Stiftung,
Anneliese Pohl Habilitationsförderung

Contact