1. Advancements in TGF-β Targeting Therapies for Head and Neck Squamous Cell Carcinoma.
- Author
-
Britton, William R., Cioffi, Isabel, Stonebraker, Corinne, Spence, Matthew, Okolo, Ogoegbunam, Martin, Cecilia, Henick, Brian, Nakagawa, Hiroshi, and Parikh, Anuraag S.
- Subjects
- *
THERAPEUTIC use of antineoplastic agents , *SQUAMOUS cell carcinoma , *CLINICAL drug trials , *PROTEINS , *CANCER , *EPITHELIAL-mesenchymal transition , *CANCER invasiveness , *HEAD & neck cancer , *IMMUNOTHERAPY , *CELLULAR signal transduction , *METASTASIS , *CANCER chemotherapy , *FIBROBLASTS , *DRUG development , *CYTOKINES , *INDIVIDUALIZED medicine , *TRANSFORMING growth factors-beta , *NEOVASCULARIZATION , *DRUG resistance - Abstract
Simple Summary: TGF-β is an important cytokine shown to drive oncogenesis in head and neck squamous cell carcinoma (HNSCC) through its diverse influences on the tumor microenvironment. While this cytokine is vital in maintaining tissue homeostasis in normal head and neck epithelia, in cancer, it paradoxically drives metastasis, angiogenesis, immune evasion, and therapy resistance. Despite promising preclinical data, the outcome of clinical trials of TGF-β inhibitors for HNSCC has been suboptimal. Patient stratification is warranted to improve this targeted therapy. Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of cancer worldwide according to GLOBOCAN estimates from 2022. Current therapy options for recurrent or metastatic disease are limited to conventional cytotoxic chemotherapy and immunotherapy, with few targeted therapy options readily available. Recent single-cell transcriptomic analyses identified TGF-β signaling as an important mediator of functional interplays between cancer-associated fibroblasts and a subset of mesenchymal cancer cells. This signaling was shown to drive invasiveness, treatment resistance, and immune evasion. These data provide renewed interest in the TGF-β pathway as an alternative therapeutic target, prompting a critical review of previous clinical data which suggest a lack of benefit from TGF-β inhibitors. While preclinical data have demonstrated the great anti-tumorigenic potential of TGF-β inhibitors, the underwhelming results of ongoing and completed clinical trials highlight the difficulty actualizing these benefits into clinical practice. This topical review will discuss the relevant preclinical and clinical findings for TGF-β inhibitors in HNSCC and will explore the potential role of patient stratification in the development of this therapeutic strategy. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF