Metabolomics

Research projects

Determining tumor lipid heterogeneity in lung cancer

The image illustrates Hematoxylin and Eosin staining (left) of lung cancer tissue, and MALDI-mass spectrometry imaging showing representative lipid species localized specifically in the tumor (right). – Reference source: Konstantinidou lab, unpublished images

Group Konstantinidou   Lung cancer is the most common cause of cancer-related deaths worldwide. Tumor-associated mutations of KRAS occur in approximately 30% of non-small cell lung cancer, the most common form of lung cancer. KRAS mutations are associated with aggressive, metastatic, and treatment-resistant cancers in both humans and mouse models. Mutant KRAS drives a complex network of lipid metabolic rearrangements to help cancer cells adapt to hypoxia and ensure their survival.
We plan to determine the changes in lipid metabolism that occur in hypoxic tumors and understand their functional significance, accounting for tumor cell-to-cell lipid heterogeneity while preserving the spatial distribution of cancer cell populations within tumors.

Targeting cellular metabolism to augment cancer therapy

Inhibition of lactate metabolism results in decreased tumorigenesis and delayed tumor growth in a genetically engineered mouse model of NSCLC. – Reference source: Deng H. et al., 2022 (https://doi.org/10.1007/s00018-022-04453-5)

Group Marti   The aim of this project is to investigate how the nucleotide/lactate metabolism and the DNA damage response machinery are associated with the tumor initiating capacity, the chemotherapy response, and the metastatic capacity of lung and mesothelioma cancer stem cells. In addition, we are exploiting treatment induced cellular adaptations as novel targets for cancer therapy.

Unravelling therapy resistance mechanisms for precision medicine in lung cancer and mesothelioma

Working model. MEKi evokes genomic and metabolic stress and triggers a protective mechanism involving PARP1. Combination of MEKi and PARPi synergistically upregulates ROS, which translates into incurable genomic and metabolic perturbations and subsequently apoptotic cell death. – Reference source: Yang H. et al., 2023 (https://pubmed.ncbi.nlm.nih.gov/36765038/)

Group Peng   Lung cancer and malignant pleural mesothelioma (MPM) are major thoracic tumors characterized by high morbidity and mortality, as well as high heterogeneity and resistance to therapy. There is an unmet need for a better understanding of the resistance mechanisms, the identification of novel targets and strategies to prevent or overcome therapeutic resistance, and the rational development of precision medicine approaches for personalized disease management to improve clinical outcomes for patients with thoracic tumors.