CRISPR screening reveals topoisomerase 1 as an immediately actionable vulnerability in cancers harboring MYC as a driver oncoprotein that can be targeted with clinically approved inhibitors.

Metabolic reprogramming of bladder cancer cells driven by mutant FGFR3 increases serine synthesis that suppresses macrophage immunostimulatory functions to generate an immunosuppressive TME, which can be overcome by targeting PI3K.

LILRB3 regulates differentiation and proliferation in acute myeloid leukemia and can be targeted with monoclonal antibodies and CAR T cells to suppress leukemia growth.

Fructose activates AMPK–mTORC1 signaling to inhibit autophagy-mediated cell death in pancreatic cancer cells caused by glucose deficiency, facilitating metabolic adaptation to the tumor microenvironment and supporting tumor growth.

LINC01089 is a super enhancer–driven long noncoding RNA that induces ERK signaling and epithelial–mesenchymal transition by regulating DIAPH3 alternative splicing that blocks N⁶-methyladenosine–mediated mRNA stabilization, establishing an epigenetic network that promotes hepatocellular carcinoma metastasis.

Identification of synthetic lethal genes with KRAS^G12Ci using genome-wide CRISPR/Cas9 screening and credentialing of the ability of TEAD inhibition to enhance KRAS^G12Ci efficacy provides a roadmap for combination strategies.

YAP1/TAZ-TEAD activation compensates for loss of KRAS effector signaling, establishing a mechanistic basis for concurrent inhibition of TEAD to enhance the efficacy of KRAS^G12C-selective inhibitor treatment of KRAS^G12C-mutant cancers.

Identification of resistance mechanisms to KRAS^G12C/SHP2 coinhibition highlights the need for additional combination therapies for lung cancer beyond on-pathway combinations and offers the basis for development of more effective combination approaches.

The poorly characterized protein kinase citron kinase is a therapeutic target in prostate cancer that drives tumor growth by regulating diverse substrates, which control several hallmarks of aggressive prostate cancer progression.

The molecular-guided therapeutic strategy of combining cabozantinib and sapanisertib restrains ERK activity to effectively suppress growth of renal cell carcinomas, including those unresponsive to immune checkpoint inhibitors.