Good news! Cancer is history (soon)!
"... FBXW7 is among the most common gene mutations in cancer, and has been linked to poor survival rates in patients. When the team cross-checked datasets, they found that mutations to the FBXW7 gene bestowed cells with a resistance to most drugs in the dataset, with lower levels of FBXW7 expression linked to worse responses to chemotherapy. ...
Cells that were deficient in FBXW7 had higher levels of mitochondrial proteins, a feature that’s been associated with drug resistance. ...
The excess proteins seemed to be stressing the mitochondria of the cancer cells, and a drug called tigecycline was found to be toxic to them by activating a process called integrated stress response (ISR). Follow-up tests with other drugs that activate ISR proved promising as well. ..."
Cells that were deficient in FBXW7 had higher levels of mitochondrial proteins, a feature that’s been associated with drug resistance. ...
The excess proteins seemed to be stressing the mitochondria of the cancer cells, and a drug called tigecycline was found to be toxic to them by activating a process called integrated stress response (ISR). Follow-up tests with other drugs that activate ISR proved promising as well. ..."
From the abstract:
"FBXW7 is one of the most frequently mutated tumor suppressors, deficiency of which has been associated with resistance to some anticancer therapies. Through bioinformatics and genome-wide CRISPR screens, we here reveal that FBXW7 deficiency leads to multidrug resistance (MDR). Proteomic analyses found an upregulation of mitochondrial factors as a hallmark of FBXW7 deficiency, which has been previously linked to chemotherapy resistance. Despite this increased expression of mitochondrial factors, functional analyses revealed that mitochondria are under stress, and genetic or chemical targeting of mitochondria is preferentially toxic for FBXW7-deficient cells. Mechanistically, the toxicity of therapies targeting mitochondrial translation such as the antibiotic tigecycline relates to the activation of the integrated stress response (ISR) in a GCN2 kinase-dependent manner. Furthermore, the discovery of additional drugs that are toxic for FBXW7-deficient cells showed that all of them unexpectedly activate a GCN2-dependent ISR regardless of their accepted mechanism of action. Our study reveals that while one of the most frequent mutations in cancer reduces the sensitivity to the vast majority of available therapies, it renders cells vulnerable to ISR-activating drugs."
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