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A targeted therapy is one that has been developed to affect a specific target, such as an enzyme or receptor. Targeted therapies can either block or increase the function of their target in order to treat a given disease; in this case, cancer.
MYC oncogene promotes tumourigenesis by coordinating cancer cell proliferation with metabolic adaptation to the consequent excessive oxidative stress. Here, the authors show that nudix hydrolase 1 (NUDT1) is a MYC-driven metabolic vulnerability and generate a NUDT1 protein degrader to treat preclinical MYC-associated cancer.
CDK4/6 inhibitors have improved outcomes for patients with ER+ breast cancer, however, those with loss of RB1 function often fail to respond. Here, the authors identify a vulnerability of ER + /RB1- breast cancer on PRMT5 and via dual blockade of ER and PRMT5 therapeutically target this in patient-derived xenograft models.
Therapeutic options for pancreatic ductal adenocarcinoma (PDAC) are limited. Here the authors report the characterization of a CEACAM6-targeting antibody drug conjugate loaded with a BET protein degrader, showing antitumour activity in PDAC preclinical models.
In this World View, H. Michael Shepard describes his personal story behind the discovery of trastuzumab, 25 years since its FDA approval for HER2-overexpressing breast cancers.
Mutant gain-of-function p53 is commonly found in human cancers. Huang, Cao, Qian et al. developed and validated the use of multifunctional biomimetic nanoreceptors that bind to and promote the degradation of mutant p53 as a cancer therapy.