Department of Internal Medicine, Memorial Healthcare System, 703 North Flamingo Road, Pembroke Pines, FL 33028, USA.
Department of Hematology and Oncology, Memorial Healthcare System, 703 North Flamingo Road, Pembroke Pines, FL 33028, USA.
Int J Mol Sci. 2024 Feb 8;25(4):2060. doi: 10.3390/ijms25042060.
In the realm of cancer therapeutics, targeting the hypoxia-inducible factor (HIF) pathway has emerged as a promising strategy. This study delves into the intricate web of HIF-associated mechanisms, exploring avenues for future anticancer therapies. Framing the investigation within the broader context of cancer progression and hypoxia response, this article aims to decipher the pivotal role played by HIF in regulating genes influencing angiogenesis, cell proliferation, and glucose metabolism. Employing diverse approaches such as HIF inhibitors, anti-angiogenic therapies, and hypoxia-activated prodrugs, the research methodologically intervenes at different nodes of the HIF pathway. Findings showcase the efficacy of agents like EZN-2968, Minnelide, and Acriflavine in modulating HIF-1α protein synthesis and destabilizing HIF-1, providing preliminary proof of HIF-1α mRNA modulation and antitumor activity. However, challenges, including toxicity, necessitate continued exploration and development, as exemplified by ongoing clinical trials. This article concludes by emphasizing the potential of targeted HIF therapies in disrupting cancer-related signaling pathways.
在癌症治疗领域，靶向缺氧诱导因子 (HIF) 途径已成为一种很有前途的策略。本研究深入探讨了 HIF 相关机制的复杂网络，探索了未来抗癌治疗的途径。本文将研究置于癌症进展和缺氧反应的更广泛背景下，旨在阐明 HIF 在调节影响血管生成、细胞增殖和葡萄糖代谢的基因方面的关键作用。本研究采用 HIF 抑制剂、抗血管生成疗法和缺氧激活前药等多种方法，在 HIF 途径的不同节点进行了方法学干预。研究结果表明，EZN-2968、Minnelide 和 Acriflavine 等药物在调节 HIF-1α 蛋白合成和破坏 HIF-1 方面具有疗效，为 HIF-1α mRNA 调节和抗肿瘤活性提供了初步证据。然而，包括毒性在内的挑战需要继续探索和开发，正在进行的临床试验就是例证。本文最后强调了靶向 HIF 治疗在破坏与癌症相关的信号通路方面的潜力。
