Saleh Tareq, Bloukh Sarah, Hasan Mira, Al Shboul Sofian
Department of Pharmacology and Public Health, Faculty of Medicine, The Hashemite University, Zarqa 13115, Jordan.
Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan.
Biochim Biophys Acta Rev Cancer. 2023 Nov;1878(6):188994. doi: 10.1016/j.bbcan.2023.188994. Epub 2023 Oct 6.
Therapy-Induced Senescence (TIS) is an established response to anticancer therapy in a variety of cancer models. Ample evidence has characterized the triggers, hallmarks, and functional outcomes of TIS in preclinical studies; however, limited evidence delineates TIS in clinical cancer (human tumor samples). We examined the literature that investigated the induction of TIS in samples derived from human cancers and highlighted the major findings that suggested that TIS represents a main constituent of tumor biology. The most frequently utilized approach to identify TIS in human cancers was to investigate the protein expression of senescence-associated markers (such as cyclins, cyclin-dependent kinase inhibitors, Ki67, DNA damage repair response markers, DEC1, and DcR1) via immunohistochemical techniques using formalin-fixed paraffin-embedded (FFPE) tissue samples and/or testing the upregulation of Senescence-Associated β-galactosidase (SA-β-gal) in frozen sections of unfixed tumor samples. Collectively, and in studies where the extent of TIS was determined, TIS was detected in 31-66% of tumors exposed to various forms of chemotherapy. Moreover, TIS was not only limited to both malignant and non-malignant components of tumoral tissue but was also identified in samples of normal (non-transformed) tissue upon chemo- or radiotherapy exposure. Nevertheless, the available evidence continues to be limited and requires a more rigorous assessment of in vivo senescence based on novel approaches and more reliable molecular signatures. The accurate assessment of TIS will be beneficial for determining its relevant contribution to the overall outcome of cancer therapy and the potential translatability of senotherapeutics.
治疗诱导的衰老（TIS）是多种癌症模型中对抗癌治疗的一种既定反应。在临床前研究中，大量证据已对TIS的触发因素、特征和功能结果进行了描述；然而，在临床癌症（人类肿瘤样本）中界定TIS的证据有限。我们查阅了研究人类癌症样本中TIS诱导情况的文献，并突出了主要发现，这些发现表明TIS是肿瘤生物学的一个主要组成部分。在人类癌症中识别TIS最常用的方法是通过免疫组织化学技术，使用福尔马林固定石蜡包埋（FFPE）组织样本研究衰老相关标志物（如细胞周期蛋白、细胞周期蛋白依赖性激酶抑制剂、Ki67、DNA损伤修复反应标志物、DEC1和DcR1）的蛋白表达，和/或在未固定肿瘤样本的冰冻切片中检测衰老相关β-半乳糖苷酶（SA-β-gal）的上调。总体而言，在确定TIS程度的研究中，在接受各种形式化疗的肿瘤中，31%-66%检测到了TIS。此外，TIS不仅限于肿瘤组织的恶性和非恶性成分，在接受化疗或放疗的正常（未转化）组织样本中也被发现。然而，现有证据仍然有限，需要基于新方法和更可靠的分子特征对体内衰老进行更严格的评估。准确评估TIS将有助于确定其对癌症治疗总体结果的相关贡献以及衰老治疗药物的潜在可转化性。
