Targeting Stress-Response Pathways and Therapeutic Resistance in Head and Neck Cancer

Abstract

Head and neck cancer is the sixth leading cancer worldwide; head and neck squamous cell carcinoma (HNSCC) accounts for more than 90% of incident cases. In the US, cases of HNSCC associated with human papillomavirus (HPV) have been growing in proportion amongst a younger demographic with superior outcomes to the same treatments, relative to cases associated with tobacco. Yet failures to improve the long-term prognosis of advanced HNSCC over the last three decades persist in part due to intrinsic and acquired mechanisms of resistance. Deregulation of the pathways to respond to stress, such as apoptosis and autophagy, often contributes to drug resistance and tumor progression. Here we review the stress-response pathways in drug response and resistance in HNSCC to explore strategies to overcome these resistance mechanisms. We focus on the mechanisms of resistance to current standard cares, such as chemotherapy (i.e., cisplatin), radiation, and cetuximab. Then, we discuss the strategies to overcome these resistances, including novel combinations and immunotherapy.

EGFR Mutations in Head and Neck Squamous Cell Carcinoma

“…One study reported that prolonged treatment with CTX promoted p27 Kip1 -mediated G1 arrest with the induction of autophagy [ 58 ]. The activation of autophagy has been shown to have opposing roles with respect to radiation response with some reports showing autophagy to be a radiosensitizer [ 59 , 60 ], while others show it plays a role in radioresistance [ 61 ]. Interestingly, a recent study found that EGFR expression and RT response depended on the human papilloma virus (HPV) status of the tumors [ 62 ].…”

Cisplatin‐induced HSF1‐HSP90 axis enhances the expression of functional PD‐L1 in oral squamous cell carcinoma

“…More than 90% of oral cancer is classified as oral squamous cell carcinoma (OSCC), with 377,713 new cases and 177,757 deaths worldwide in 2020. 1 , 2 Together with surgery, chemotherapy in combination with radiotherapy for OSCC have been developed in the past couple of decades. Cisplatin (CDDP), the most classic platinum‐based cytotoxic agent adapted to various types of malignancies, remains a pivotally important chemotherapeutic drug for OSCC.…”

“…Head and neck cancer is the sixth most commonly diagnosed cancer worldwide, and oral cancer is the most frequent tumor of the head and neck region. More than 90% of oral cancer is classified as oral squamous cell carcinoma (OSCC), with 377,713 new cases and 177,757 deaths worldwide in 2020 1,2 . Together with surgery, chemotherapy in combination with radiotherapy for OSCC have been developed in the past couple of decades.…”

“…More than 90% of oral cancer is classified as oral squamous cell carcinoma (OSCC), with 377,713 new cases and 177,757 deaths worldwide in 2020. 1,2 Together with surgery, chemotherapy…”

Orofacial squamous cell carcinoma: Analysis of histopathological reports of 465 patients in Tanzania

“…Malignant conditions in the orofacial region constitute an important group of human diseases with an estimated prevalence of about 5-8% of all malignancies worldwide, and squamous cell carcinoma accounts for up to 90% of all these lesions in the head and neck region. [1][2][3] Orofacial squamous cell carcinoma (OfSCC) originates from the mucosal epithelium in the aerodigestive tract (oral cavity, pharynx, and sinuses) [4] and keratinocytes in the spinous layer of the epidermis (skin). [5] Generally, OfSCC tends to affect more males than females by twofold to fourfold, with the median age of diagnosis being around 60 years, though, the incidence of OfSCC in persons under the age of 45 years is increasing.…”