Protecting Against Postsurgery Oral Cancer Recurrence with an Implantable Hydrogel Vaccine for In Situ Photoimmunotherapy.

Oral squamous cell carcinoma (OSCC) often recurs aggressively and metastasizes despite surgery and adjuvant therapy, driven by postoperative residual cancer cells near the primary tumor site. An implantable in situ vaccine hydrogel was designed to target residual OSCC cells post-tumor removal. This hydrogel serves as a reservoir for the sustained localized release of δ-aminolevulinic acid (δ-ALA), enhancing protoporphyrin IX-mediated photodynamic therapy (PDT), and a polydopamine-hyaluronic acid composite for photothermal therapy (PTT).

Selective ligand recognition and activation of somatostatin receptors SSTR1 and SSTR3.

Somatostatin receptors (SSTRs) exert critical biological functions such as negatively regulating hormone release and cell proliferation, making them popular targets for developing therapeutics to treat endocrine disorders, especially neuroendocrine tumors. Although several panagonists mimicking the endogenous ligand somatostatin are available, the development of more effective and safer somatostatinergic therapies is limited due to a lack of molecular understanding of the ligand recognition and regulation of divergent SSTR subtypes. Here, we report four cryoelectron microscopy structures of G-coupled SSTR1 and SSTR3 activated by distinct agonists, including the FDA-approved panagonist pasireotide as well as their selective small molecule agonists L-797591 and L-796778.

A human mucosal melanoma organoid platform for modeling tumor heterogeneity and exploring immunotherapy combination options.

Mucosal melanoma (MM), an aggressive rare subtype of melanoma, is distinct from cutaneous melanoma and has poor prognoses. We addressed the lack of cell models for MM by establishing 30 organoids of human oral MM (OMM), which retained major histopathological and functional features of parental tumors. Organoid groups derived from chronologically or intratumorally distinct lesions within the same individual displayed heterogeneous genetics, expression profiles, and drug responses, indicating rapid tumor evolution and poor clinical response.

Single-cell and spatial dissection of precancerous lesions underlying the initiation process of oral squamous cell carcinoma.

Precancerous lesions of the oral mucosa, especially those accompanied by moderate to severe dysplasia, contribute to the initiation of oral squamous cell carcinoma (OSCC). However, the cellular compositions and spatial organization of the precancerous stage and how these factors promote human OSCC initiation remain unclear. Here, we built a single-cell transcriptome atlas and a spatial transcriptome map after obtaining data from pairwise human oral mucosal biopsies of 9 individuals consisting of very early-stage OSCC, adjacent precancerous lesions with moderate to severe dysplasia, as well as a matched normal region.

A biomimetic nanoplatform for customized photothermal therapy of HNSCC evaluated on patient-derived xenograft models.

Cancer cell membrane (CCM) derived nanotechnology functionalizes nanoparticles (NPs) to recognize homologous cells, exhibiting translational potential in accurate tumor therapy. However, these nanoplatforms are majorly generated from fixed cell lines and are typically evaluated in cell line-derived subcutaneous-xenografts (CDX), ignoring the tumor heterogeneity and differentiation from inter- and intra- individuals and microenvironments between heterotopic- and orthotopic-tumors, limiting the therapeutic efficiency of such nanoplatforms. Herein, various biomimetic nanoplatforms (CCM-modified gold@Carbon, i.

A Physiologically Responsive Nanocomposite Hydrogel for Treatment of Head and Neck Squamous Cell Carcinoma via Proteolysis-Targeting Chimeras Enhanced Immunotherapy.

Although immunotherapy has revolutionized oncotherapy, only ≈15% of head and neck squamous cell carcinoma (HNSCC) patients benefit from the current therapies. An immunosuppressive tumor microenvironment (TME) and dysregulation of the polycomb ring finger oncogene BMI1 are potential reasons for the failure. Herein, to promote immunotherapeutic efficacy against HNSCC, an injectable nanocomposite hydrogel is developed with a polymer framework (PLGA-PEG-PLGA) that is loaded with both imiquimod encapsulated CaCO nanoparticles (RC) and cancer cell membrane (CCM)-coated mesoporous silica nanoparticles containing a peptide-based proteolysis-targeting chimeras (PROTAC) for BMI1 and paclitaxel (PepM@PacC).

Small-molecule PROTAC mediates targeted protein degradation to treat STAT3-dependent epithelial cancer.

The aberrant activation of STAT3 is associated with the etiology and progression in a variety of malignant epithelial-derived tumors, including head and neck squamous cell carcinoma (HNSCC) and colorectal cancer (CRC). Due to the lack of an enzymatic catalytic site or a ligand-binding pocket, there are no small-molecule inhibitors directly targeting STAT3 that have been approved for clinical translation. Emerging proteolysis targeting chimeric (PROTAC) technology-based approach represents a potential strategy to overcome the limitations of conventional inhibitors and inhibit activation of STAT3 and downstream genes.

Pharmacogenomic landscape of head and neck squamous cell carcinoma informs precision oncology therapy.

Head and neck squamous cell carcinoma (HNSCC) is a common and frequently lethal cancer with few therapeutic options. In particular, there are few effective targeted therapies. Development of highly effective therapeutic strategies tailored to patients with HNSCC remains a pressing challenge.

Clinical utility of PDX cohorts to reveal biomarkers of intrinsic resistance and clonal architecture changes underlying acquired resistance to cetuximab in HNSCC.

Cetuximab is a widely used drug for treating head and neck squamous cell carcinomas (HNSCCs); however, it provides restricted clinical benefits, and its response duration is limited by drug resistance. Here, we conducted randomized "Phase II-like clinical trials" of 49 HNSCC PDX models and reveal multiple informative biomarkers for intrinsic resistance to cetuximab (e.g.

Plasma Messenger RNAs Identified Through Bioinformatics Analysis are Novel, Non-Invasive Prostate Cancer Biomarkers.

Aim: To identify new biomarkers of prostate cancer (PCa) for the diagnosis and prediction of clinical outcomes.

Materials And Methods: Existing microarray data of PCa tissues in the Oncomine database were analyzed and candidate differentially expressed genes (DEGs) that may be novel and noninvasive biomarkers were obtained. On this basis, plasma mRNA was extracted from PCa patients and healthy donors.

Right Cu S@MnS Core-Shell Nanoparticles as a Photo/HO-Responsive Platform for Effective Cancer Theranostics.

Stimuli-responsive nanomedicines have become a recent research focus as a candidate for cancer treatment because of their effectiveness, sensibility, and minimal invasiveness. In this work, a novel nanosystem is developed based on Cu S@MnS core-shell nanoparticles (CSNPs) in which the Cu S core serves as a photosensitizer to generate hyperthermia and reactive oxygen species (ROS), and the MnS shell is used in HO-responsive O production. Cu S@MnS CSNPs with an independent core and shell ratio are synthesized by a controllable hot-injection method, resulting in an optimal photothermal (PT) effect with a PT conversion efficiency of up to 47.

Analysis of Mucosal Melanoma Whole-Genome Landscapes Reveals Clinically Relevant Genomic Aberrations.

Purpose: Unlike advances in the genomics-driven precision treatment of cutaneous melanomas, the current poor understanding of the molecular basis of mucosal melanomas (MM) has hindered such progress for MM patients. Thus, we sought to characterize the genomic landscape of MM to identify genomic alterations with prognostic and/or therapeutic implications.

Experimental Design: Whole-genome sequencing (WGS) was performed on 65 MM samples, including 63 paired tumor blood samples and 2 matched lymph node metastases, with a further droplet digital PCR-based validation study of an independent MM cohort ( = 80).