Researchers from Chimerix, now part of Jazz Pharmaceuticals, presented preclinical data on ONC-206, a compound that functions as both an agonist of the mitochondrial protease Caseinolytic peptidase P (CLPP) and an antagonist of the G protein-coupled receptor DRD2, in models of triple-negative breast cancer (TNBC).
Although hormone receptor-positive (HR+) breast cancer accounts for over 70% of cases, 20%-30% of patients still experience relapse despite endocrine therapies such as tamoxifen. Recurrence is also observed in HER2+ breast cancer, even with HER2-targeted antibodies and antibody-drug conjugates (ADCs), the use of which can be limited by adverse effects such as interstitial lung disease.
Beigene Co. Ltd. has presented data on a CDK4 selective inhibitor, BGB-43395, for the potential treatment of this cancer type and which would reduce the neutropenia associated with CDK6 inhibition.
In tumoral cells, the modulation of the G1/S phases of cell cycle is destabilized by amplification and high expression of cyclin E (CCNE) or by mutation or loss of retinoblastoma 1 (RB1) gene. Cancer cells meeting these characteristics have been sown to be highly sensitive to cyclin-dependent kinase 2 (CDK2) depletion.
Cyclins and cyclin-dependent kinases (CDKs) regulate the activity of E2F and Rb to drive cell cycle progression. Disrupting this interaction has shown lethality in cancer cells harboring alterations that lead to higher expression of E2F1.
Researchers from Mbrace Therapeutics Inc. presented the discovery and preclinical evaluation of MBRC-101, a novel antibody-drug conjugate (ADC) targeting the membrane-associated tyrosine kinase receptor EphA5, being developed for the treatment of cancer.
Retinoic acid receptor-γ (RARγ) agonism is a key factor in CD8 T-cell-mediated immunity to infectious pathogens. The lack of studies on the effects of RARγ agonists on in vivo tumor growth of triple-negative (TNBC) or HER2+ breast cancers make it necessary to investigate whether RARγ could play a critical role in T-cell-mediated immunity in these breast cancers, using novel RARγ nuclear agonists.
PI3Kα H1047R accounts for one-third of all PI3Kα mutations and is associated with treatment resistance to targeted therapies in breast cancer treatment. In addition, treatment with selective PI3Kα inhibitors often results in significant adverse events such as hyperglycemia due to on-target toxicity.
Researchers from Bridgebio Pharma Inc. recently presented BBO-10203, a first-in-class, orally bioavailable, covalent small-molecule candidate designed to inhibit RAS-driven PI3Kα activity without affecting glucose metabolism.
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