Hypoxia-induced molecular alterations and druggable targets in triple negative breast cancer cell lines - HipTNBC

1. To perform bioinformatics analysis in publicly available TNBC multi-omics data sets (TCGA, METABRIC) for identification of novel acute continuous and cycling hypoxia-associated molecular alterations (potential biomarkers) and relevant druggable targets.
2. To verify molecular alterations identified in bioinformatics analysis, as well as 15-gene expression continuous acute hypoxia signature and cycling hypoxia signature in the panel of triple negative breast cancer-reference cell lines (TNBC-RCLs) exposed to various modes of hypoxia. 
3. To explore the transcriptomic and proteomic expression status of various isoforms of HIFs (HIF-1, HIF2, HIF-3) during exposure of TNBC-RCLs to various modes of hypoxia. 
4. To identify mitochondrial apoptotic dependencies induced by various hypoxia conditions for identification of druggable targets for BH3 mimetics. 
5. To explore the effects of various modes of hypoxia on the sensitivity of TNBC-RCLs to the pharmacological agents identified in the bioinformatics and mitochondrial apoptotic priming dependency analysis.

Benefit for society: the results of the project will help to improve future treatment choices, care, survival, and health-related quality of life for patients with aggressive and difficult-to-treat breast cancer.

Issues the project will address: 'hypoxia' refers to conditions in which oxygen does not reach the cells in sufficient quantities. Normal cells usually die, but malignant cells can adapt to these conditions and survive. The project will find out how cells that survive hypoxia differ from other cells and how to destroy them effectively.

Possible solutions: To find out how hypoxic survivors (cells) differ from dead cells; we will grow breast cancer cells under low oxygen conditions and identify which gene programmes are triggered by these conditions and how cancer cells escape death.