{"title":"三重打击方法:蛋氨酸限制增强脑转移性三阴性乳腺癌的联合抑制剂。","authors":"Samyuktha Suresh,James M Ford","doi":"10.1172/jci193171","DOIUrl":null,"url":null,"abstract":"Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, presents a clinical challenge in developing effective treatment options. In this issue of the JCI, Zeng et al. demonstrate a provocative and promising therapeutic strategy for TNBC by leveraging the metabolic vulnerabilities presented by methylthioadenosine phosphorylase (MTAP) deletion to genotoxic stress inducers, such as poly (ADP-ribose) polymerase inhibitors (PARPi). They found that combining MTAP deletion or inhibition with PARPi was highly effective in brain metastatic TNBC where the methionine-limited environment further enhanced this combination. This approach underscores the importance of targeting metabolic vulnerabilities in the development of personalized cancer therapies.","PeriodicalId":520097,"journal":{"name":"The Journal of Clinical Investigation","volume":"9 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A triple-punch approach: methionine restriction enhances combination inhibitors in brain metastatic triple-negative breast cancer.\",\"authors\":\"Samyuktha Suresh,James M Ford\",\"doi\":\"10.1172/jci193171\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, presents a clinical challenge in developing effective treatment options. In this issue of the JCI, Zeng et al. demonstrate a provocative and promising therapeutic strategy for TNBC by leveraging the metabolic vulnerabilities presented by methylthioadenosine phosphorylase (MTAP) deletion to genotoxic stress inducers, such as poly (ADP-ribose) polymerase inhibitors (PARPi). They found that combining MTAP deletion or inhibition with PARPi was highly effective in brain metastatic TNBC where the methionine-limited environment further enhanced this combination. This approach underscores the importance of targeting metabolic vulnerabilities in the development of personalized cancer therapies.\",\"PeriodicalId\":520097,\"journal\":{\"name\":\"The Journal of Clinical Investigation\",\"volume\":\"9 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The Journal of Clinical Investigation\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1172/jci193171\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Journal of Clinical Investigation","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1172/jci193171","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
A triple-punch approach: methionine restriction enhances combination inhibitors in brain metastatic triple-negative breast cancer.
Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, presents a clinical challenge in developing effective treatment options. In this issue of the JCI, Zeng et al. demonstrate a provocative and promising therapeutic strategy for TNBC by leveraging the metabolic vulnerabilities presented by methylthioadenosine phosphorylase (MTAP) deletion to genotoxic stress inducers, such as poly (ADP-ribose) polymerase inhibitors (PARPi). They found that combining MTAP deletion or inhibition with PARPi was highly effective in brain metastatic TNBC where the methionine-limited environment further enhanced this combination. This approach underscores the importance of targeting metabolic vulnerabilities in the development of personalized cancer therapies.