Preclinical models of HNSCC and their role in drug discovery - an emphasis on the cancer microenvironment and microbiota.

Introduction: Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide. Treatment options and patient outcomes have not improved significantly over the past decades, increasing the need for better preclinical models. Holistic approaches that include an intact and functional immune compartment along with the patient's individual tumor microbiome will help improve the predictive value of novel drug efficacy.

Correction: Becker et al. Identifying Predictive Biomarkers for Head and Neck Squamous Cell Carcinoma Response. 2023, , 5597.

In the original publication [...

Combined inhibition of EZH2 and CDK4/6 perturbs endoplasmic reticulum-mitochondrial homeostasis and increases antitumor activity against glioblastoma.

He, we show that combined use of the EZH2 inhibitor GSK126 and the CDK4/6 inhibitor abemaciclib synergistically enhances antitumoral effects in preclinical GBM models. Dual blockade led to HIF1α upregulation and CalR translocation, accompanied by massive impairment of mitochondrial function. Basal oxygen consumption rate, ATP synthesis, and maximal mitochondrial respiration decreased, confirming disrupted endoplasmic reticulum-mitochondrial homeostasis.

p16 overexpression identifies oncogenic high-risk HPV infection in non-oropharyngeal squamous cell carcinoma of the head and neck.

Background: Human papillomavirus (HPV) is an increasing risk factor for cancer. HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) is associated with a favorable outcome. Blockstaining for p16 is a surrogate marker for HPV+ OPSCC.

Differential Expression of CKLF-like MARVEL Transmembrane Domain-Containing Protein 6 and Programmed Cell Death Ligand 1 as Prognostic Biomarkers in Upper Tract Urothelial Carcinoma.

Upper tract urothelial carcinoma (UTUC) accounts for 5-10% of all UCs. Immune checkpoint inhibitors (ICIs) have been established for UCs. The prognostic and predictive potential of programmed cell death ligand 1 (PD-L1) expression to stratify patients benefiting from ICIs is not fully understood, and additional markers influencing the impact of PD-L1-mediated ICI response are needed.

Diagnosis of differentiated dysplasia as a variant of oral epithelial dysplasia.

Objectives: The World Health Organization's definition of oral epithelial dysplasia includes differentiated dysplasia, which is defined by purely architectural abnormalities of oral mucosa without cytological changes. We analysed differentiated dysplasia's frequency, progression risk and correlation with oral brush cytology.

Materials And Methods: Cytoarchitectural criteria and expression patterns of keratin 13/17 and ki67 were studied in oral biopsies clinically diagnosed with leukoplakia.

Identifying Predictive Biomarkers for Head and Neck Squamous Cell Carcinoma Response.

The 5-year survival rate for head and neck squamous cell carcinoma (HNSCC) is approximately 65%. In addition to radio-chemotherapy, immunotherapy is an approach in the treatment of advanced HNSCC. A better understanding of the immune context would allow personalized treatment by identifying patients who are best suited for different treatment options.

Establishing safe high hydrostatic pressure devitalization thresholds for autologous head and neck cancer vaccination and reconstruction.

High hydrostatic pressure specifically devitalizes cells and tissues without major changes in their molecular structure. Hence, high hydrostatic pressure may enhance the development of whole-cell anti-tumor vaccines, representing tumor heterogeneity and thus (neo-) antigen diversity. Moreover, safe devitalization of tumor-infiltrated supporting tissue may facilitate reimplantation for functional reconstruction.

Evaluation of the Cellular Dissociation Grading, Based on Tumor Budding and Cell Nest Size, in Squamous Cell Carcinoma of the Penis.

The "Cellular Dissociation Grade" (CDG) is based on tumor cell budding and cell nest size. Many studies have examined the CDG in squamous cell carcinomas of other organs such as the lungs, oral cavity, pharynx, larynx, cervix and esophagus. In this study, the CDG was examined in 109 cases of invasive penile squamous cell carcinoma that were treated at the University Medicine Rostock between 2014 and 2022.

Preclinical Head and Neck Squamous Cell Carcinoma Models for Combined Targeted Therapy Approaches.

This study aimed to refine combined targeted approaches on well-characterized, low-passage tumor models. Upon in vivo xenografting in immunodeficient mice, three cell lines from locally advanced or metastatic HNSCC were established. Following quality control and basic characterization, drug response was examined after therapy with 5-FU, Cisplatin, and cyclin-dependent kinase inhibitors (abemaciclib, THZ1).

Clinical characteristics, treatment outcomes and potential novel therapeutic options for patients with neuroendocrine carcinoma of the prostate.

Background: Neuroendocrine carcinomas of the prostate (NEPCs) are rare tumors with poor prognosis. While platinum and etoposide-based chemotherapy regimens (PE) are commonly applied in first-line for advanced disease, evidence for second-line therapy and beyond is very limited.

Methods: Retrospective analysis of all patients with NEPCs including mixed differentiation with adenocarcinoma component and well differentiated neuroendocrine tumors (NETs, carcinoids) at two high-volume oncological centers between 12/2000 and 11/2017.