{"doi":"10.3390/ijms26041752","title":"Emerging Role of Hypoxia-Inducible Factors (HIFs) in Modulating Autophagy: Perspectives on Cancer Therapy","abstract":"<jats:p>Hypoxia-inducible factors (HIFs) are master regulators of cellular responses to low oxygen levels and modulate autophagy, a conserved process essential for maintaining homeostasis. Under hypoxic conditions, HIFs regulate the expression of autophagy-related genes and influence autophagic flux and cellular stress responses. Dysregulated hypoxia-induced autophagy promotes cancer cell survival, metabolism, and metastasis, thereby contributing to treatment resistance. Targeting HIF-mediated pathways or modulating autophagic processes offers the potential to improve traditional cancer therapies and overcome drug resistance. Pharmacological inhibitors of HIFs or autophagy, either alone or in combination with other treatments, may disrupt the pro-survival mechanisms within the hypoxic tumor microenvironment. Further research is needed to elucidate the intricate interplay between HIF signaling and the autophagy machinery in cancer cells. Understanding these processes could pave the way for novel therapeutic strategies to enhance treatment outcomes and combat drug resistance. This review highlights the complex relationship between HIFs and autophagy in cancer development and therapy, offering insights into how targeting these pathways may improve patient outcomes.</jats:p>","journal":"International Journal of Molecular Sciences","year":2025,"id":622232,"datarank":0.4887144807032224,"base_score":3.258096538021482,"endowment":3.258096538021482,"self_citation_contribution":0.4887144807032224,"citation_network_contribution":0.0,"self_endowment_contribution":0.4887144807032224,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1607593,"name":"Maroua Jalouli","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Emerging Role of Hypoxia-Inducible Factors (HIFs) in Modulating Autophagy: Perspectives on Cancer Therapy","abstract":"<jats:p>Hypoxia-inducible factors (HIFs) are master regulators of cellular responses to low oxygen levels and modulate autophagy, a conserved process essential for maintaining homeostasis. Under hypoxic conditions, HIFs regulate the expression of autophagy-related genes and influence autophagic flux and cellular stress responses. Dysregulated hypoxia-induced autophagy promotes cancer cell survival, metabolism, and metastasis, thereby contributing to treatment resistance. Targeting HIF-mediated pathways or modulating autophagic processes offers the potential to improve traditional cancer therapies and overcome drug resistance. Pharmacological inhibitors of HIFs or autophagy, either alone or in combination with other treatments, may disrupt the pro-survival mechanisms within the hypoxic tumor microenvironment. Further research is needed to elucidate the intricate interplay between HIF signaling and the autophagy machinery in cancer cells. Understanding these processes could pave the way for novel therapeutic strategies to enhance treatment outcomes and combat drug resistance. This review highlights the complex relationship between HIFs and autophagy in cancer development and therapy, offering insights into how targeting these pathways may improve patient outcomes.</jats:p>","is_dataset_classified":null,"base_score":3.258096538021482,"endowment":3.258096538021482,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40004215","pmcid":"PMC11855875","openalex_id":"https://openalex.org/W4407754499","authors":[],"funders":[{"funder_name":"Imam Mohammad Ibn Saud Islamic University (IMSIU)","grant_id":"IMSIU-DDRSP2501","title":null}],"total_grants":1,"fwci":18.4824,"citation_percentile":0.99529544,"influential_citations":0,"citation_trend":[{"year":2025,"count":13},{"year":2026,"count":12}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/1422-0067/26/4/1752/pdf?version=1739941786","host_type":"journal"},{"url":"https://www.mdpi.com/1422-0067/26/4/1752/pdf?version=1739941786","host_type":"publisher"},{"url":"https://www.mdpi.com/1422-0067/26/4/1752/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/ijms26041752","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40004215","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11855875","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11855875","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11855875?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Autophagy in Disease and Therapy","Cancer, Hypoxia, and Metabolism","RNA modifications and cancer","Humans","Autophagy","Neoplasms","Animals","Signal Transduction","Tumor Microenvironment","Basic Helix-Loop-Helix Proteins","Hypoxia-Inducible Factor 1","Drug Resistance, Neoplasm"],"mesh_terms":["Animals","Antineoplastic Agents","Autophagy","Humans","Neoplasms","Signal Transduction","Drug Resistance, Neoplasm","Basic Helix-Loop-Helix Transcription Factors","Basic Helix-Loop-Helix Proteins","Hypoxia-Inducible Factor 1","Tumor Microenvironment"],"keywords":["Autophagy","Hypoxia (environmental)","Biology","Hypoxia-inducible factors","Cancer cell","Cellular adaptation","Tumor microenvironment","Cancer research","Cell biology","Cancer","Chemistry","Gene","Biochemistry","Tumor cells","Apoptosis","Genetics","Drug resistance","Cancer therapy","Tumor Progression"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T18:46:03.716513Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}