Altered Mechanobiology of PDAC Cells with Acquired Chemoresistance to Gemcitabine and Paclitaxel.

: Pancreatic ductal adenocarcinoma acquired resistance to chemotherapy poses a major limitation to patient survival. Despite understanding some biological mechanisms of chemoresistance, much about those mechanisms remains to be uncovered. Mechanobiology, which studies the physical properties of cells, holds promise as a potential target for addressing the challenges of chemoresistance in PDAC.

The effect of cancer-associated mutations on ligand binding and receptor function - A case for the 5-HT receptor.

The serotonin 5-HT receptor is a G protein-coupled receptor (GPCR) mainly expressed in the central nervous system. Besides regulating mood, appetite, and reproductive behavior, it has been identified as a potential target for cancer treatment. In this study, we aimed to investigate the effects of cancer patient-derived 5-HT receptor mutations on ligand binding and receptor functionality.

TCR-Engineered T Cells Directed against Ropporin-1 Constitute a Safe and Effective Treatment for Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) has an urgent need for new therapies. We discovered Ropporin-1 (ROPN1) as a target to treat TNBC with T cells. ROPN1 showed high and homogenous expression in 90% of primary and metastatic TNBC but not in healthy tissues.

CD3-engaging bispecific antibodies trigger a paracrine regulated wave of T-cell recruitment for effective tumor killing.

The mechanism of action of bispecific antibodies (bsAbs) directing T-cell immunity to solid tumors is incompletely understood. Here, we screened a series of CD3xHER2 bsAbs using extracellular matrix (ECM) embedded breast cancer tumoroid arrays exposed to healthy donor-derived T-cells. An initial phase of random T-cell movement throughout the ECM (day 1-2), was followed by a bsAb-dependent phase of active T-cell recruitment to tumoroids (day 2-4), and tumoroid killing (day 4-6).