{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T02:05:27Z","timestamp":1792461927539,"version":"4.5.0"},"reference-count":211,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20132018R1A5A2023127"],"award-info":[{"award-number":["NRF\u20132018R1A5A2023127"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor that regulates the transcription of many genes that are responsible for the adaptation and survival of tumor cells in hypoxic environments. Over the past few decades, tremendous efforts have been made to comprehensively understand the role of HIF-1 in tumor progression. Based on the pivotal roles of HIF-1 in tumor biology, many HIF-1 inhibitors interrupting expression, stabilization, DNA binding properties, or transcriptional activity have been identified as potential therapeutic agents for various cancers, yet none of these inhibitors have yet been successfully translated into clinically available cancer treatments. In this review, we briefly introduce the regulation of the HIF-1 pathway and summarize its roles in tumor cell proliferation, angiogenesis, and metastasis. In addition, we explore the implications of HIF-1 in the development of drug resistance and cancer-related pain: the most commonly encountered obstacles during conventional anticancer therapies. Finally, the current status of HIF-1 inhibitors in clinical trials and their perspectives are highlighted, along with their modes of action. This review provides new insights into novel anticancer drug development targeting HIF-1. HIF-1 inhibitors may be promising combinational therapeutic interventions to improve the efficacy of current cancer treatments and reduce drug resistance and cancer-related pain.<\/jats:p>","DOI":"10.3390\/cancers14246054","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T03:23:49Z","timestamp":1670556229000},"page":"6054","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":167,"title":["Hypoxia-Inducible Factor-1: A Novel Therapeutic Target for the Management of Cancer, Drug Resistance, and Cancer-Related Pain"],"prefix":"10.3390","volume":"14","author":[{"given":"Bich Phuong","family":"Bui","sequence":"first","affiliation":[{"name":"College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University\u2013Seoul, Dongguk-ro 32, Ilsandong-gu, Goyang 10326, Gyeonggi, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phuong Linh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University\u2013Seoul, Dongguk-ro 32, Ilsandong-gu, Goyang 10326, Gyeonggi, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyeong","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University\u2013Seoul, Dongguk-ro 32, Ilsandong-gu, Goyang 10326, Gyeonggi, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jungsook","family":"Cho","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University\u2013Seoul, Dongguk-ro 32, Ilsandong-gu, Goyang 10326, Gyeonggi, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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