局部晚期鳞状细胞头颈癌（LA SCCHN）患者的标准治疗是手术后进行化学放疗（CRT）或定向CRT。然而，约50％的LA SCCHN患者在完成治疗后的两年内会出现疾病复发或转移，这些患者的预后不良。尽管如此，LA SCCHN的当前治疗方案已经超过20年未经修改，迫切需要新的治疗方案。疾病复发的主要原因之一是治疗抗性，这通常是由癌细胞逃避凋亡的能力引起的。逃避凋亡部分归因于抑制凋亡蛋白（IAPs）的过量表达。包括X-联锁IAP（XIAP）和细胞IAP 1和2（cIAP1 / 2）在内的IAPs是一类调节内源性和外源性凋亡途径引起的凋亡的蛋白质。 IAPs已被证明在SCCHN中过度表达，与不良临床预后有关，因此是一个合理的治疗靶点。迄今为止，已经研究了多种IAP抑制剂；然而，只有一个名为xevinapant的强效口服小分子IAP抑制剂在与CRT联合应用时显示了临床的概念证明。具体来说，在未切除的LA SCCHN患者的随机、双盲、第二期试验中，xevinapant显示出与安慰剂+ CRT相比的优越疗效。在这里，我们描述了LA SCCHN的当前治疗方案，并提出了靶向IAPs的理由以及xevinapant的临床数据。版权所有©2023年作者。由Elsevier Ltd.发布。保留所有权利。

Standard of care for patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) is surgery followed by chemoradiotherapy (CRT) or definitive CRT. However, approximately 50 % of patients with LA SCCHN develop disease recurrence or metastasis within 2 years of completing treatment, and the outcome for these patients is poor. Despite this, the current treatment landscape for LA SCCHN has remained relatively unchanged for more than 2 decades, and novel treatment options are urgently required. One of the key causes of disease recurrence is treatment resistance, which commonly occurs due to cancer cells' ability to evade apoptosis. Evasion of apoptosis has been in part attributed to the overexpression of inhibitor of apoptosis proteins (IAPs). IAPs, including X-linked IAP (XIAP) and cellular IAP 1 and 2 (cIAP1/2), are a class of proteins that regulate apoptosis induced by intrinsic and extrinsic apoptotic pathways. IAPs have been shown to be overexpressed in SCCHN, are associated with poor clinical outcomes, and are, therefore, a rational therapeutic target. To date, several IAP inhibitors have been investigated; however, only xevinapant, a potent, oral, small-molecule IAP inhibitor, has shown clinical proof of concept when combined with CRT. Specifically, xevinapant demonstrated superior efficacy in combination with CRT vs placebo + CRT in a randomized, double-blind, phase 2 trial in patients with unresected LA SCCHN. Here, we describe the current treatment landscape in LA SCCHN and provide the rationale for targeting IAPs and the clinical data reported for xevinapant.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.