Multicenter Analysis of Genomically Targeted Single Patient Use Requests for Pediatric Neoplasms.

Purpose: The US Food and Drug Administration-expanded access program (EAP) uses a single patient use (SPU) mechanism to provide patient access to investigational agents in situations where no satisfactory or comparable therapy is available. Genomic profiling of de novo and relapsed or refractory childhood cancer has led to increased identification of new drug targets in the last decade. The aim of this study is to examine the SPU experience for genomically targeted therapies in patients with pediatric cancer.

CD244 represents a new therapeutic target in head and neck squamous cell carcinoma.

Background: Developing novel strategies to overcome the immunosuppressive tumor microenvironment is a critically important area of cancer therapy research. Here, we assess the therapeutic potential of CD244 (2B4/signaling lymphocyte activation molecule family 4), an immunoregulatory receptor found on a variety of immune cells, including exhausted CD8 T cells, dendritic cells (DCs), and myeloid-derived suppressor cells (MDSCs).

Methods: Using de-identified human tumor and blood samples from patients with head and neck squamous cell carcinoma (HNSCC) and HNSCC models in WT and CD244 mice, we assessed the therapeutic potential of CD244 using flow cytometry, RT-PCR, Luminex immunoassays and histopathological analyses.

The Emerging Role of CD244 Signaling in Immune Cells of the Tumor Microenvironment.

In cancer, immune exhaustion contributes to the immunosuppressive tumor microenvironment. Exhausted immune cells demonstrate poor effector function and sustained expression of certain immunomodulatory receptors, which can be therapeutically targeted. CD244 is a Signaling Lymphocyte Activation Molecule (SLAM) family immunoregulatory receptor found on many immune cell types-including NK cells, a subset of T cells, DCs, and MDSCs-that represents a potential therapeutic target.

Malignant peripheral nerve sheath tumor: Transformation in a patient with neurofibromatosis type 2.

Malignant peripheral nerve sheath tumor (MPNST) is a rare soft-tissue sarcoma with an unfavorable prognosis and limited therapeutic options. MPNSTs can be sporadic, but are often associated with neurofibromatosis (NF) 1 and usually arise from preexisting neurofibromas. MPNSTs in patients with NF2 have been reported in only exceedingly rare cases, and the mechanisms underlying transformation into an MPNST have not been fully elucidated.

Pazopanib therapy for desmoid tumors in adolescent and young adult patients.

Background: Desmoid tumors/aggressive fibromatosis (DT/AF) lack a reliably effective medical therapy. Surgical resection may be morbid and does not preclude recurrence. Radiation may carry severe late effects, particularly detrimental in young patients.

The TRPV1 receptor is associated with preferential stress in large dorsal root ganglion neurons in early diabetic sensory neuropathy.

Chronic diabetic neuropathy is associated with peripheral demyelination and degeneration of nerve fibers. The mechanism(s) underlying neuronal injury in diabetic sensory neuropathy remain poorly understood. Recently, we reported increased expression and function of transient receptor potential vanilloid 1 (TRPV1) in large dorsal root ganglion (DRG) neurons in diabetic sensory neuropathy.