The development of KRAS G12D inhibitors has proven challenging to date and, different from anti-KRAS G12C strategies, no compound targeting KRAS G12D mutation has been approved so far.

Previous studies have demonstrated that the natural product isotoosendanin (ITSN) inhibited triple-negative breast cancer (TNBC) metastasis by preventing epithelial-mesenchymal transition (EMT) and lamellipodia formation regulated by the TGF-β–Smad2/3 signaling pathway in TNBC cells through directly binding to TGF-β receptor type 1 (TGF-βR1).

Plexium Inc. has reported the discovery and preclinical characterization of PLX-3618, a novel monovalent direct degrader of BRD4 being developed for the treatment of cancer.

Tumor cells use metabolic reprogramming for their survival and to fuel and boost their proliferation. Only 15% of patients with colorectal cancer (CRC) benefit from immune checkpoint blockade therapy, mainly due to tumor microenvironment changes to promote CD8+ T-cell exhaustion and inactivation allowing tumor cells to escape from immunity.

Mutations in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) induce tumorigenesis due to generation of the oncometabolite (R)-2-hydroxyglutarate (R-2HG). A hallmark of solid tumors carrying mutations in IDH1 is immune evasion by T-cell exclusion and altered epigenetic state. Researchers from the Center for Cancer Research, Massachusetts General Hospital have published a study in Science on July 12, 2024, in which they demonstrate that inhibiting mutant IDH1 restored antitumoral immunity.