One of the functions of tumor-associated macrophages (TAMS) is to protect the tumor against the immune system, inhibiting T-cell engagement and reducing the efficacy of checkpoint inhibitors. Polyamidoamine hydroxyl dendrimers (HDs) target TAM without the need of a targeting ligand and are retained by TAMs for up to 1 month allowing radiation to deposit in the tumor.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, primarily due to its dense, desmoplastic and immunosuppressive tumor microenvironment (TME) that hinders the efficacy of immune checkpoint inhibitors such as anti-programmed cell death 1 (PD-1).
Carbonic anhydrase IX (CAIX, CA9) is a membrane-associated isoform of the α-carbonic anhydrase enzyme family, involved in pH regulation and the acidification of the tumor microenvironment (TME) in solid tumors. It is widely recognized as a marker of tumor hypoxia and serves as a prognostic indicator in multiple human cancers.
Esophageal cancer is a malignant disease with high incidence and mortality, where esophageal squamous cell carcinoma (ESCC) is the most common histological subtype. To improve therapeutic approaches for ESCC, it is key to explore the mechanisms behind the disease and find targeted inhibitors.
The OX40/OX40L costimulatory pathway is crucial for effective T-cell activation and is inducibly expressed in response to immunological stimulation. Targeting OX40L has demonstrated safety and efficacy in preclinical studies using nonhuman primate models of kidney and heart transplantation.
Heartbeat.bio AG and Biotx.ai GmbH have partnered to identify and validate novel therapeutic targets in heart failure. The collaboration combines Biotx.ai’s causal mapping of the genome for target discovery with Heartbeat.bio’s human-based Cardioid drug discovery platform.
Researchers at Cincinnati Children’s Hospital Medical Center have developed a new human cell model for VEXAS syndrome, a rare, severe disorder marked by systemic inflammation, bone marrow failure and high mortality. VEXAS (short for vacuoles, E1-enzyme, X-linked, autoinflammatory, somatic) is a recently identified, acquired clonal hematopoietic disease that often co-occurs with myelodysplastic syndrome.
Degradation is a therapeutic strategy that could offer possibilities to get at currently undruggable target proteins. In targeted degradation, compounds induce interactions between a target protein and a protein that can tag the target for degradation. In principle, there are several pathways that could be used for such tagging; the most attention has gone to ubiquitin ligases, in particular cereblon, a protein that is part of a ubiquitin ligase complex and the target of several approved drugs.
The first systematic whole genome sequencing study of how chemotherapy damages healthy tissues has shown that many, but not all, of these agents cause mutations and premature aging of normal blood cells.
Additional early-stage research and drug discovery news in brief, from: Alpha Cognition, Audiocure Pharma, Inflectis Bioscience, Inventiva, Mira Pharmaceuticals.
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