Dual inhibition of HERs and PD-1 counteract resistance in KRAS-mutant head and neck cancer.

Background: Basket clinical trials targeting the KRAS-mutation in solid tumors have shown initial promise, including in orphan KRAS head and neck cancer (HNC). However, development of resistance to KRAS-mutant-specific inhibitors (KRASi) remains a major obstacle. Here, we investigated the intrinsic (tumor-cell autonomus) and tumor-microenvironment (TME) mechanisms of resistance to the KRASi-MRTX849 and AMG510 in a unique syngenic murine KRAS-mutated HNC cell line.

Unravelling the Complexity of HNSCC Using Single-Cell Transcriptomics.

Background/objectives: Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous and the most common form of head and neck cancer, posing significant challenges for disease management. The objective of this review is to assess the utility of single-cell RNA sequencing (scRNAseq) in addressing these challenges by enabling a detailed characterization of the tumor microenvironment (TME) at the cellular level.

Methods: This review compiles and analyzes current strategies that utilize scRNAseq and other single-cell technologies in HNSCC research.

Activation of the EGFR/PI3K/AKT pathway limits the efficacy of trametinib treatment in head and neck cancer.

Blocking the mitogen-activated protein kinase (MAPK) pathway with the MEK1/2 inhibitor trametinib has produced promising results in patients with head and neck squamous cell carcinoma (HNSCC). In the current study, we showed that trametinib treatment leads to overexpression and activation of the epidermal growth factor receptor (EGFR) in HNSCC cell lines and patient-derived xenografts. Knockdown of EGFR improved trametinib treatment efficacy both in vitro and in vivo.