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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.
The relevance of post-translational modifications in pancreatic cancer remains insufficiently explored. Here, the authors report that ZDHHC20-mediated S-Palmitoylation of the m6A reader YTHDF3 stabilizes MYC mRNA to promote the progression of KRAS-mutant pancreatic cancer.
Puissant and colleagues identify a myeloid-restricted PIK3CG/p110γ–PIK3R5/p101 axis as a therapeutic vulnerability in acute myeloid leukemia and develop a proteolysis-targeting chimera to potently degrade PIK3CG and suppress AML progression.
Two studies published concurrently in Nature report the development and preclinical activity of RMC-7977, a multi-selective inhibitor targeting the active, GTP-bound form of RAS.
Dias et al. have shown that intentional further activation of oncogenic signalling rather than its inhibition represents an alternative strategy leading to colorectal cancer cell death with tumour suppressive acquired resistance.
Effectively targeting deregulated KRAS signaling remains an unmet clinical need, as current approaches commonly lead to the development of chemoresistance in clinical settings. ADAM9-mediated lysosomal KRAS degradation is now shown to counteract PDAC chemoresistance independently of mutational status.