cabozantinib and dactolisib

A significant fraction of patients with advanced prostate cancer treated with androgen deprivation therapy experience relapse with relentless progression to lethal metastatic castration-resistant prostate cancer (mCRPC). Immune checkpoint blockade using antibodies against cytotoxic-T-lymphocyte-associated protein 4 (CTLA4) or programmed cell death 1/programmed cell death 1 ligand 1 (PD1/PD-L1) generates durable therapeutic responses in a significant subset of patients across a variety of cancer types. However, mCRPC showed overwhelming de novo resistance to immune checkpoint blockade, motivating a search for targeted therapies that overcome this resistance. Myeloid-derived suppressor cells (MDSCs) are known to play important roles in tumour immune evasion. The abundance of circulating MDSCs correlates with prostate-specific antigen levels and metastasis in patients with prostate cancer. Mouse models of prostate cancer show that MDSCs (CD11b

Topics: Anilides; Animals; CD8-Positive T-Lymphocytes; Chimera; Cytokines; Disease Models, Animal; Drug Synergism; Female; Humans; Imidazoles; Immunotherapy; Lymphocytes, Tumor-Infiltrating; Male; Mice; Molecular Targeted Therapy; Myeloid-Derived Suppressor Cells; Phosphoinositide-3 Kinase Inhibitors; Prostatic Neoplasms, Castration-Resistant; Pyridines; Quinolines; Signal Transduction; Tumor Microenvironment