Current and potential inflammation targeted therapies in head and neck cancer

Abstract

Inflammation often exists in the tumor microenvironment and is induced by inflammatory mediators (cytokines, chemokines, and growth factors) produced by the tumor, stroma, and infiltrating cells. These factors modulate tissue remodeling and angiogenesis and actively promote tumor cell survival and chemoresistance through autocrine and paracrine mechanisms. Head and neck squamous cell carcinomas (HNSCCs) are highly inflammatory and aggressive in nature, and they express a number of cytokines and growth factors involved in inflammation. These cytokines and growth factors activate important signal transduction pathways, including NF-κB, JAK/STAT, and PI3K/Akt/mTOR, which regulate the expression of genes controlling growth, survival, and chemosensitivity. This review provides an update on recent advances in the understanding of the mechanisms driving cancer-related inflammation in HNSCC and on molecular targeted therapies under pre-clinical and clinical investigation.

Smoking at Diagnosis Is an Independent Prognostic Factor for Cancer-Specific Survival in Head and Neck Cancer: Findings from a Large, Population-Based Study

“…Squamous cell head and neck carcinomas are highly inflammatory in nature and express a number of cytokines and growth factors involved in inflammation (47). Specifically, pretreatment serum IL6 levels have been found to predict recurrence and poor survival in head and neck cancer (48); smoking is associated with high IL6 levels, and this may result from the adverse effects of smoking on sleep patterns (49).…”

The JAK/STAT signaling cascade in gastric carcinoma (Review)

“…Several immunomodulatory molecules are also regulated by the JAK/STAT cascade. Specifically, reduced Th1-dominated antitumor response on aberrant STAT3 activation contributes to cancer cell survival and proliferation, suggesting the role of STAT3 in the maintenance of the tumor microenvironment by contributing to the process of inflammation and angiogenesis (77,(80)(81)(82).…”

Garcinol, a Polyisoprenylated Benzophenone Modulates Multiple Proinflammatory Signaling Cascades Leading to the Suppression of Growth and Survival of Head and Neck Carcinoma

“…Several dysregulated proinflammatory signaling cascades including NF-kB, STAT3, and serine/threonine protein kinase B (AKT) have been linked to the carcinogenesis of HNSCC and play a pivotal role in the growth, proliferation, and survival of the head and neck cancer (6)(7)(8)(9)(10). For example, Sen and colleagues recently reported that STAT3 activation can even contribute to EGF receptor inhibitor resistance in HNSCC and thereby targeting of STAT3 may represent an effective treatment strategy (10).…”