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Researchers have identified a potential new way to tackle treatment-resistant triple-negative breast cancer (TNBC)<\/a> by exploiting the disease\u2019s ability to adapt.<\/p>\n A team at MUSC Hollings Cancer Center<\/a> found that a protein called lysyl oxidase (LOX) plays an unexpected role inside TNBC cells, helping them produce energy, maintain healthy mitochondria and withstand stress.<\/p>\n The study<\/a>\u00a0suggests that blocking LOX could weaken cancer cells and make them vulnerable to a second treatment. In several preclinical models, the two-drug approach significantly slowed tumour growth without the use of chemotherapy<\/a>.<\/p>\n \u201cIt\u2019s a one-two-punch approach,\u201d said Dr Ozgur Sahin, Co-leader of the Hollings Cancer Biology and Immunology Research Program. \u201cFirst, we block LOX, which weakens the cancer cells. As they adapt and become dependent on a backup survival pathway, we deliver the second punch by blocking that pathway, too.\u201d<\/p>\n Targeting cancer from within<\/p>\n TNBC is an aggressive form of breast cancer that lacks three common molecular targets used to treat other breast cancer subtypes. This leaves patients with fewer treatment avenues, with chemotherapy being their main treatment option.<\/p>\n \u201cTriple-negative breast cancer is one of the most aggressive, deadliest versions of breast cancer,\u201d Dr Sahin said. \u201cChemotherapy is really the mainstay, and interestingly, this subtype is sensitive to chemotherapy compared to others, but resistance develops quite quickly.\u201d<\/p>\n Sahin\u2019s laboratory has previously studied LOX for its role outside cancer cells, where it can alter the tissue surrounding tumours. However, the new research found that the protein also supports survival inside TNBC cells.<\/p>\n \u201cLOX helps cancer cells keep multiple survival systems running. When we blocked LOX, the cancer cells lost that advantage,\u201d explained postdoctoral fellow Dr Burge Ulukan, the study\u2019s co-first author. \u201cWhen we inhibit it, we are inhibiting multiple arms. We\u2019re disrupting cells\u2019 energy production and making them much more vulnerable to treatment.\u201d<\/p>\n Turning a weakness into a weapon<\/p>\n The researchers then looked for a way to exploit the weakness created by blocking LOX. They focused on ferroptosis, a form of cell death caused by toxic damage within cells.<\/p>\n Blocking LOX weakened two of the cancer cells\u2019 defences against ferroptosis and the cells responded by becoming more dependent on another defence controlled by Dihydroorotate dehydrogenase (DHODH).<\/p>\n