Solid tumors create a distinctive acidic microenvironment due to their rapid growth and altered metabolic processes. This acidosis is a critical component of tumor biology with a pH range between 6,5 - 6,9, influencing cancer progression and therapy response. This PhD study is dedicated to unraveling the complexities of tissue acidosis and its specific implications on epithelial cancer cells.
Key Research Objectives:
1. Acidosis Characterization: Investigate and characterize the effects of acidic microenvironment in solid tumors, on a panel of epithelial cancer cells.
2. Cellular Responses: Delve into the molecular and functional responses of epithelial cancer cells to tissue acidosis. This will involve studying changes in gene expression, protein function, and alterations in cellular behavior under acidosis conditions.
3. Tumor Progression: Examine the role of tissue acidosis in various facets of tumor progression, including cell proliferation, invasion, and resistance to therapies. Understand how acidosis contributes to the aggressiveness of epithelial cancers.
4. Therapeutic Insights: Explore potential strategies for exploitning the acidic tumor microenvironment, with the aim of enhancing cancer treatment outcomes.
The focus of the research is on basic cellular signaling, with a particular interest in the role of protein kinases and phosphatases in regulating MAP kinase signaling in human cancer. This includes the study of classical MAP kinases, such as p38 MAPK (MAPK14), as well as atypical MAPK kinases, such as ERK3 (MAPK6) and ERK4 (MAPK4). Additionally, the research examines negative regulators of MAP kinases, such as the family of MAP kinase phosphatases.