Clinical value of monoclonal antibodies and tyrosine kinase inhibitors in the treatment of head and neck squamous cell carcinoma

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of malignant tumours that affects over 500,000 patients per year. Treatment failure is generally due to the heterogeneity of these tumours and to the serious adverse effects associated with treatment. Immunological system impairment, which is common in HNSCC, further contributes to treatment failure by mediating tumour escape mechanisms. To date, the only clinically approved targeted therapy agent is cetuximab, a monoclonal antibody (mAb) that binds to, and inhibits, epidermal growth factor receptor, which is widely overexpressed in HNSCC. Cetuximab has been proven to induce antibody-dependent cellular cytotoxicity, further magnifying its therapeutic effect. DNA sequencing of HNSCC cells has identified the presence of mutated genes, thus making their protein products potential targets for therapeutic inhibition. Immune mechanisms have been found to have a significant impact on carcinogenesis, thus providing the rationale to support efforts to identify anticancer compounds with immunomodulatory properties. In the context of the rapid development of novel targeted agents, the aim of the present paper is to review our current understanding of HNSCC and to review the novel anticancer agents (mAbs and TKIs) introduced in recent years, including an assessment of their efficacy and mechanisms of action.

The current state of molecular testing in the treatment of patients with solid tumors, 2019

“…Activation of other EGFR family members (HER2, HER3) can play a role in this resistance, as can c‐MET, insulin growth factor receptor (IGFR), and PI3K . PIK3CA is frequently mutated in HNSCC and plays a key role in the progression of HNSCC . Targeted agents against all these markers have been developed and have undergone or are undergoing various phases of clinical testing.…”

“…94 PIK3CA is frequently mutated in HNSCC and plays a key role in the progression of HNSCC. 95,96 Targeted agents against all these markers have been developed and have undergone or are undergoing various phases of clinical testing. Human papillomavirus (HPV)-related HNSCCs are increasing in incidence and have different oncogenic processes compared with HPVunrelated HNSCCs.…”

Molecular Basis of Modern Targeted Therapy for Squamous Cell Carcinoma of the Tongue and Oral Mucosa With Monoclonal Antibodies

“…У млекопитающих известно 58 рецепторных тирозинки-наз (РТК), разделенных на 20 семейств, которые имеют схожее строение: внутриклеточная часть представлена достаточно консервативными субдоменами тирозин-киназы, которые отделены трансмембранным доменом от собственно рецепторной экстрацеллюлярной части молекулы [7]. Первым трансмембранным белком, у ко-торого были открыты тирозинкиназные свойства, был рецептор эпидермального ростового фактора EGFR (ERBB1, HER1) [8].…”

Potencjał fukoidyny jako środka wspomagającego w terapii onkologicznej

“…Najczęściej stosowanymi lekami w chorobach nowotworowych nadal pozostają chemioterapeutyki, takie jak pochodne platyny, taksanów czy antybiotyki peptydowe jak bleomycyna. Obecnie coraz bardziej popularne w leczeniu stają się inhibitory kinaz tyrozynowych i przeciwciała monoklonalne, których użycie umożliwia ograniczenie występowania poważnych działań niepożądanych poprzez zmniejszenie ogólnoustrojowej toksyczności terapii [52].…”