Perspectives on targeted therapy of larynx cancer

Larynx cancer is a type of head and neck cancer that originates from laryngeal epithelium. It is one of the most common cancers affecting the upper aerodigestive tract and its main subtype is laryngeal squamous cell carcinoma (LSCC). Currently, the annual incidence of larynx cancer is about ۱۸۴,۶۱۵ people worldwide. The disease has a higher prevalence rate in men and is mostly associated with tobacco use and excessive alcohol consumption. Human papillomavirus (HPV) has also been considered, as another risk factor for some kinds of laryngeal cancer. Similar to most other cancers, the molecular alterations in larynx cancer include dysregulation of cellular survival and proliferation, cell-cycle regulation, and abnormal cellular differentiation. These altered molecular processes involved mutations and abnormal expression levels in several proteins including P۵۳, Cyclin D۱, P۲۱, EGFR, E-cadherin, PTEN, NOTCH, PIK۳CA, FGFR۳, JAK۳, MET, FBXW۷, etc. In addition, several non-coding RNAs including microRNAs and long non-coding RNAs (lncRNAs) have been implicated in the progression and metastasis of laryngeal cancers and can be targeted as a novel therapeutic solution. A recent study reveals that a circular RNA, circPARD۳ suppresses autophagy in laryngeal squamous cell carcinoma and promotes LSCC malignant progression and chemoresistance. Therefore, the complicated genetic and epigenetic heterogeneity involved in larynx cancer leads to difficulties in therapy. Advancements in tumor molecular biology have led to improvements in the treatment approaches. Besides traditional and novel surgical tumor removal methods, chemotherapy, radiotherapy, immunotherapy, and photo-immunotherapy have been reported as available therapeutic approaches for larynx cancer. Presently, some of the commonly used chemo-drugs for laryngeal cancers include Cisplatin, Carboplatin, and ۵-fluorouracil (۵-FU). However, due to the unsuccessful and imperfect outcomes of the previous approaches, targeted therapy has received significant attention in the context of larynx cancer personalized medicine. In this case, several drugs such as Cetuximab, Pembrolizumab, and Nivolumab have also been suggested and used as targeted solutions for larynx cancer. Cetuximab, known as Erbitux, is a monoclonal antibody targeted against epidermal growth factor receptor (EGFR) and used successfully in combination with radiotherapy for larynx cancer treatment. Moreover, Pembrolizumab (Keytruda) and Nivolumab (Opdivo) are monoclonal antibodies that work as immune checkpoint inhibitors. They block programmed cell death protein ۱ (PD-۱) and activate T cells to fight tumor cells. Consequently, due to advancements in cancer molecular biology and immunology, the discovery of novel targeted drugs against laryngeal cancer is rapidly expanding. For example, a recent study suggests that SAHA, a histone deacetylase inhibitor, could be a potential targeted therapy for laryngeal cancer cells.

کلیدواژه ها:

larynx cancer ، targeted therapy ، clinical trials ، molecular pathways