Kleszcz Robert
Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, 4, Święcickiego Str., 60-781 Poznan, Poland.
Cancers (Basel). 2023 Aug 24;15(17):4247. doi: 10.3390/cancers15174247.
The molecular initiators of Head and Heck Squamous Cell Carcinoma (HNSCC) are complex. Human Papillomavirus (HPV) infection is linked to an increasing number of HNSCC cases, but HPV-positive tumors generally have a good prognosis. External factors that promote the development of HPV-negative HNSCC include tobacco use, excessive alcohol consumption, and proinflammatory poor oral hygiene. On a molecular level, several events, including the well-known overexpression of epidermal growth factor receptors (EGFR) and related downstream signaling pathways, contribute to the development of HNSCC. Conventional chemotherapy is insufficient for many patients. Thus, molecular-based therapy for HNSCC offers patients a better chance at a cure. The first molecular target for therapy of HNSCC was EGFR, inhibited by monoclonal antibody cetuximab, but its use in monotherapy is insufficient and induces resistance. This article describes attempts at combinatorial molecular targeted therapy of HNSCC based on several molecular targets and exemplary drugs/drug candidates. The new concept of anakoinosis-based therapy, which means treatment that targets the intercellular and intracellular communication of cancer cells, is thought to be the way to improve the clinical outcome for HNSCC patients. The identification of a link between molecular targeted therapy and anakoinosis raises the potential for further progress in HPV-negative HNSCC therapy.
头颈部鳞状细胞癌(HNSCC)的分子引发因素较为复杂。人乳头瘤病毒(HPV)感染与越来越多的HNSCC病例相关,但HPV阳性肿瘤通常预后良好。促进HPV阴性HNSCC发展的外部因素包括吸烟、过度饮酒以及炎症性口腔卫生不良。在分子水平上,包括表皮生长因子受体(EGFR)的众所周知的过表达及相关下游信号通路在内的多个事件,都促成了HNSCC的发展。传统化疗对许多患者而言并不充分。因此,基于分子的HNSCC治疗为患者提供了更好的治愈机会。HNSCC治疗的首个分子靶点是EGFR,可被单克隆抗体西妥昔单抗抑制,但其单药治疗并不充分且会诱导耐药。本文描述了基于多个分子靶点及示例性药物/候选药物对头颈部鳞状细胞癌进行联合分子靶向治疗的尝试。基于细胞间和细胞内癌细胞通讯进行治疗的基于“交互适应失调”的治疗新概念,被认为是改善HNSCC患者临床结局的途径。分子靶向治疗与交互适应失调之间联系的确定,为HPV阴性HNSCC治疗取得进一步进展带来了可能性。