Co-clinical Trial of Novel Bispecific Anti-HER2 Antibody Zanidatamab in Patient-Derived Xenografts.

Unlabelled: Zanidatamab is a bispecific human epidermal growth factor receptor 2 (HER2)-targeted antibody that has demonstrated antitumor activity in a broad range of HER2-amplified/expressing solid tumors. We determined the antitumor activity of zanidatamab in patient-derived xenograft (PDX) models developed from pretreatment or postprogression biopsies on the first-in-human zanidatamab phase I study (NCT02892123). Of 36 tumors implanted, 19 PDX models were established (52.

Limited Independent Follow-Up with Germline Testing of Variants Detected in and by Tumor-Only Sequencing.

Introduction: Genomic profiling is performed in patients with advanced or metastatic cancer, in order to direct cancer treatment, often sequencing tumor-only, without a matched germline comparator. However, because many of the genes analyzed on tumor profiling overlap with those known to be associated with hereditary cancer predisposition syndromes (HCPS), tumor-only profiling can unknowingly uncover germline pathogenic (P) and likely pathogenic variants (LPV). In this study, we evaluated the number of patients with P/LPVs identified in and () via tumor-only profiling, then determined the germline testing outcomes for those patients.

HER2-low expression in patients with advanced or metastatic solid tumors.

Background: Human epidermal growth factor receptor 2 (HER2)-low is a newly defined category with HER2 1+ or 2+ expression by immunohistochemistry (IHC) and lack of HER2 gene amplification measured by in situ hybridization (ISH). Much remains unknown about the HER2-low status across tumor types and changes in HER2 status between primary and metastatic samples.

Patients And Methods: HER2 expression by IHC was evaluated in 4701 patients with solid tumors.

Caspase-8 loss radiosensitizes head and neck squamous cell carcinoma to SMAC mimetic-induced necroptosis.

Caspase-8 (CASP8) is one of the most frequently mutated genes in head and neck squamous carcinomas (HNSCCs), and CASP8 mutations are associated with poor survival. The distribution of these mutations in HNSCCs suggests that they are likely to be inactivating. Inhibition of CASP8 has been reported to sensitize cancer cells to necroptosis, a regulated cell death mechanism.

Pancreatic cancer microenvironment: a current dilemma.

Pancreatic cancer is one of the leading causes of cancer-related death in the United States and survival outcomes remain dismal despite significant advances in molecular diagnostics and therapeutics in clinical practice. The microenvironment of pancreatic cancer carries unique features with increased desmoplastic reaction and is infiltrated by regulatory T cells and myeloid-derived suppressor cells which negatively impact the effector immune cells. Current evidence suggests that stellate cell-induced hypovascular stroma may have direct effects on aggressive behavior of pancreatic cancer.