Department of Physiology, Faculty of Medicine, Masaryk University / Kamenice 5, CZ-625 00, Brno, Czech Republic.
Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00, Brno, Czech Republic.
Cell Death Dis. 2021 Feb 18;12(2):192. doi: 10.1038/s41419-021-03474-5.
Many cancer therapies aim to trigger apoptosis in cancer cells. Nevertheless, the presence of oncogenic alterations in these cells and distorted composition of tumour microenvironment largely limit the clinical efficacy of this type of therapy. Luckily, scientific consensus describes about 10 different cell death subroutines with different regulatory pathways and cancer cells are probably not able to avoid all of cell death types at once. Therefore, a focused and individualised therapy is needed to address the specific advantages and disadvantages of individual tumours. Although much is known about apoptosis, therapeutic opportunities of other cell death pathways are often neglected. Molecular heterogeneity of head and neck squamous cell carcinomas (HNSCC) causing unpredictability of the clinical response represents a grave challenge for oncologists and seems to be a critical component of treatment response. The large proportion of this clinical heterogeneity probably lies in alterations of cell death pathways. How exactly cells die is very important because the predominant type of cell death can have multiple impacts on the therapeutic response as cell death itself acts as a second messenger. In this review, we discuss the different types of programmed cell death (PCD), their connection with HNSCC pathogenesis and possible therapeutic windows that result from specific sensitivity to some form of PCD in some clinically relevant subgroups of HNSCC.
许多癌症疗法旨在诱导癌细胞凋亡。然而，这些细胞中存在致癌改变和肿瘤微环境组成的扭曲，在很大程度上限制了这种类型治疗的临床疗效。幸运的是，科学共识描述了大约 10 种不同的细胞死亡程序，具有不同的调节途径，癌细胞可能无法一次避免所有的细胞死亡类型。因此，需要针对个体肿瘤的特定优势和劣势进行有针对性和个体化的治疗。尽管人们对细胞凋亡有了很多了解，但其他细胞死亡途径的治疗机会往往被忽视。头颈部鳞状细胞癌（HNSCC）的分子异质性导致临床反应的不可预测性，这对头颈肿瘤学家来说是一个严峻的挑战，似乎是治疗反应的一个关键组成部分。这种临床异质性的很大一部分可能在于细胞死亡途径的改变。细胞的确切死亡方式非常重要，因为细胞死亡本身作为第二信使，主要的细胞死亡类型可能会对治疗反应产生多种影响。在这篇综述中，我们讨论了不同类型的程序性细胞死亡（PCD），它们与 HNSCC 发病机制的关系，以及在一些临床上相关的 HNSCC 亚组中，由于对某种形式的 PCD 具有特定的敏感性而产生的可能的治疗窗口。
