Postgraduate Program in Dentistry, Federal University of Santa Catarina, Florianópolis, Brazil.
Department of Morphological Sciences, Biological Sciences Center, Federal University of Santa Catarina, Florianópolis, Brazil.
Oral Oncol. 2022 Sep;132:105979. doi: 10.1016/j.oraloncology.2022.105979. Epub 2022 Jul 8.
The purpose of this review was to summarise available literature concerning the anticancer effects of both putative and validated BH3-mimetics in head and neck squamous cell carcinomas. A literature search was performed and studies assessing malignant cell lines, xenograft models, and/or humans were considered eligible. A total of 501 studies were identified, of which 40 were included. One phase-II clinical trial assessing gossypol (combined with docetaxel) was found. The remaining 39 preclinical studies investigated cell lines and/or xenograft models involving the use of six validated BH3-mimetics (A-1210477, A-1331852, ABT-737, navitoclax, S63845, venetoclax) and six putative BH3-mimetics (ApoG2, gossypol, obatoclax, sabutoclax, TW-37, and YC137). In preclinical settings, most validated BH3-mimetics were capable of inducing apoptosis (in-vitro) and tumour growth inhibition (in-vivo). The majority of putative BH3-mimetics were also capable of inducing cell death, although important off-target effects, such as autophagy induction, were also described. Combinations with conventional anticancer drugs, ionising radiation, or multiple BH3-mimetics generally resulted in enhanced anticancer effects, such as increased sensitivity to apoptotic stimuli, especially considering some cell lines that showed resistance to either treatment alone. In conclusion, although clinical data are still insufficient to evaluate the anticancer effects of BH3-mimetics in head and neck squamous cell carcinomas, promising results in preclinical settings were observed concerning induction of cell death and inhibition of tumour growth. Therefore, further clinical trials are highly encouraged.
本次综述的目的在于总结已发表的关于潜在和已验证的 BH3 模拟物在头颈部鳞状细胞癌中的抗癌作用的文献。进行了文献检索，评估了恶性细胞系、异种移植模型和/或人类的研究被认为符合条件。共确定了 501 项研究，其中有 40 项被纳入。发现了一项评估棉酚（与多西紫杉醇联合使用）的 II 期临床试验。其余 39 项临床前研究调查了涉及使用六种已验证的 BH3 模拟物（A-1210477、A-1331852、ABT-737、navitoclax、S63845、venetoclax）和六种潜在 BH3 模拟物（ApoG2、棉酚、obatoclax、sabutoclax、TW-37 和 YC137）的细胞系和/或异种移植模型。在临床前环境中，大多数已验证的 BH3 模拟物能够诱导细胞凋亡（体外）和肿瘤生长抑制（体内）。大多数潜在的 BH3 模拟物也能够诱导细胞死亡，尽管也描述了重要的脱靶效应，如自噬诱导。与传统抗癌药物、电离辐射或多种 BH3 模拟物的联合通常会产生增强的抗癌作用，例如增加对凋亡刺激的敏感性，尤其是考虑到一些细胞系对单独治疗表现出耐药性。总之，尽管临床数据仍然不足以评估 BH3 模拟物对头颈部鳞状细胞癌的抗癌作用，但在临床前研究中观察到了诱导细胞死亡和抑制肿瘤生长的有希望的结果。因此，强烈鼓励进行进一步的临床试验。
