Research Projects

Recent evidence suggests that cancer cells have a "lipolytic phenotype" due to their reliance on the Fatty acid Oxidation (FAO) pathway for energy needs, balancing ROs levels, survival, and proliferation during metabolic stress. This phenotype is also linked to drug resistance, metastatic progression, and immune suppression. Cancer cells from adipocyte-rich environments, such as breast and ovarian, are more likely to adopt this lipolytic phenotype. The mitochondria and peroxisomes are prime sites for the fatty acid β-Oxidation pathway in eukaryotic cells. Peroxisome fatty acid oxidation involves stepwise shortening of fatty acyl-CoA to acetyl-CoA, which is then transferred to mitochondria for full oxidation to CO2 and H2O. The peroxisome interplay with other subcellular organelles, especially mitochondria, plays a critical role in energy metabolism during stress and malignancy. Recent evidence correlating enhanced FAO metabolism in response to anti-cancer therapies suggests the possible involvement of FAO with drug resistance. Targeting mitochondrial FAO through CPT1a inhibition can inhibit long-chain fatty acid transport and subsequent oxidation in the mitochondrial matrix. Targeting peroxisomal FAO is an attractive strategy for developing novel therapies. The proposed study aims to understand the significance of peroxisomal fatty acid oxidation during cellular adaptation to metabolic stress and how this lipolytic phenotype contributes to cancer cell resistance to tamoxifen therapy.