Rapid progress in molecular cancer biology coupled with the discovery of novel oncology drugs has opened new horizons for cancer target discovery. As one of the crucial signaling pathways related to tumorigenesis, hypoxia-inducible factor-1 (HIF-1) coordinates the activity of many transcription factors and their downstream molecules that impact tumor growth and metastasis. Accumulating evidence suggests that the transcriptional responses to acute hypoxia are mainly attributable to HIF-1α. Moreover, the overexpression of HIF-1α in several solid cancers has been found to be strongly associated with poor prognosis. Thus, pharmacological targeting of the HIF-1 signaling pathways has been considered as a new strategy for cancer therapy in the recent years. Although over the past decade, tremendous efforts have been made in preclinical studies to develop new HIF-1 inhibitors from natural products (reservoirs of novel therapeutic agents), to date, these efforts have not been successfully translated into clinically available treatments. In this review, we provide new insights into the bio-pharmacological considerations for selecting natural compounds as potential HIF-1 inhibitors to accelerate anti-cancer drug development. In addition, we highlighted the importance of assessing the dependency of cancer on HIF1A to shortlist cancer types as suitable disease models. This may subsequently lead to new paradigms for discovering more HIF-1 inhibitors derived from natural products and facilitate the development of potent therapeutic agents targeting specific cancer types.

分子癌症生物学的快速进展以及新型肿瘤药物的发现为癌症靶点的发现开辟了新的视野。作为与肿瘤发生相关的关键信号通路之一，缺氧诱导因子-1 (HIF-1) 协调许多影响肿瘤生长和转移的转录因子及其下游分子的活性。越来越多的证据表明，对急性缺氧的转录反应主要归因于 HIF-1α。此外，已发现 HIF-1α 在几种实体癌中的过表达与预后不良密切相关。因此，近年来，HIF-1信号通路的药理学靶向已被认为是一种新的癌症治疗策略。尽管在过去的十年里，在临床前研究中已经做出了巨大的努力，以从天然产物（新型治疗药物的储存库）中开发新的 HIF-1 抑制剂，迄今为止，这些努力尚未成功地转化为临床可用的治疗方法。在这篇综述中，我们对选择天然化合物作为潜在的 HIF-1 抑制剂以加速抗癌药物开发的生物药理学考虑提供了新的见解。此外，我们强调了评估癌症对 我们为选择天然化合物作为潜在的 HIF-1 抑制剂以加速抗癌药物开发的生物药理学考虑提供了新的见解。此外，我们强调了评估癌症对 我们为选择天然化合物作为潜在的 HIF-1 抑制剂以加速抗癌药物开发的生物药理学考虑提供了新的见解。此外，我们强调了评估癌症对HIF1A将癌症类型列为合适的疾病模型。这可能随后导致发现更多源自天然产物的 HIF-1 抑制剂的新范例，并促进针对特定癌症类型的有效治疗剂的开发。