The hypoxia-inducible factor-1α in stemness and resistance to chemotherapy in gastric cancer: Future directions for therapeutic targeting
Hypoxia-inducible factor-1α (HIF-1α) is a crucial mediator of intra-tumoral heterogeneity, tumor progression, and unresponsiveness to therapy in tumors with hypoxia. Gastric tumors, one of the most aggressive tumors in the clinic, are highly enriched in hypoxic niches, and the degree of hypoxia is s...
| Main Author: | |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-02-01
|
| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2023.1082057/full |
| _version_ | 1811169472982024192 |
|---|---|
| author | Gulnihal Ozcan Gulnihal Ozcan |
| author_facet | Gulnihal Ozcan Gulnihal Ozcan |
| author_sort | Gulnihal Ozcan |
| collection | DOAJ |
| description | Hypoxia-inducible factor-1α (HIF-1α) is a crucial mediator of intra-tumoral heterogeneity, tumor progression, and unresponsiveness to therapy in tumors with hypoxia. Gastric tumors, one of the most aggressive tumors in the clinic, are highly enriched in hypoxic niches, and the degree of hypoxia is strongly correlated with poor survival in gastric cancer patients. Stemness and chemoresistance in gastric cancer are the two root causes of poor patient outcomes. Based on the pivotal role of HIF-1α in stemness and chemoresistance in gastric cancer, the interest in identifying critical molecular targets and strategies for surpassing the action of HIF-1α is expanding. Despite that, the understanding of HIF-1α induced signaling in gastric cancer is far from complete, and the development of efficacious HIF-1α inhibitors bears various challenges. Hence, here we review the molecular mechanisms by which HIF-1α signaling stimulates stemness and chemoresistance in gastric cancer, with the clinical efforts and challenges to translate anti-HIF-1α strategies into the clinic. |
| first_indexed | 2024-04-10T16:42:58Z |
| format | Article |
| id | doaj.art-24f99c99bfde4f76a7877b077ccc17be |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-10T16:42:58Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-24f99c99bfde4f76a7877b077ccc17be2023-02-08T04:29:36ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-02-011110.3389/fcell.2023.10820571082057The hypoxia-inducible factor-1α in stemness and resistance to chemotherapy in gastric cancer: Future directions for therapeutic targetingGulnihal Ozcan0Gulnihal Ozcan1Department of Medical Pharmacology, School of Medicine, Koç University, Istanbul, TurkiyeKoç University Research Center for Translational Medicine, Istanbul, TurkiyeHypoxia-inducible factor-1α (HIF-1α) is a crucial mediator of intra-tumoral heterogeneity, tumor progression, and unresponsiveness to therapy in tumors with hypoxia. Gastric tumors, one of the most aggressive tumors in the clinic, are highly enriched in hypoxic niches, and the degree of hypoxia is strongly correlated with poor survival in gastric cancer patients. Stemness and chemoresistance in gastric cancer are the two root causes of poor patient outcomes. Based on the pivotal role of HIF-1α in stemness and chemoresistance in gastric cancer, the interest in identifying critical molecular targets and strategies for surpassing the action of HIF-1α is expanding. Despite that, the understanding of HIF-1α induced signaling in gastric cancer is far from complete, and the development of efficacious HIF-1α inhibitors bears various challenges. Hence, here we review the molecular mechanisms by which HIF-1α signaling stimulates stemness and chemoresistance in gastric cancer, with the clinical efforts and challenges to translate anti-HIF-1α strategies into the clinic.https://www.frontiersin.org/articles/10.3389/fcell.2023.1082057/fullhypoxia-inducible factor-1αgastric cancerstemnesschemoresistancederegulated signaling |
| spellingShingle | Gulnihal Ozcan Gulnihal Ozcan The hypoxia-inducible factor-1α in stemness and resistance to chemotherapy in gastric cancer: Future directions for therapeutic targeting Frontiers in Cell and Developmental Biology hypoxia-inducible factor-1α gastric cancer stemness chemoresistance deregulated signaling |
| title | The hypoxia-inducible factor-1α in stemness and resistance to chemotherapy in gastric cancer: Future directions for therapeutic targeting |
| title_full | The hypoxia-inducible factor-1α in stemness and resistance to chemotherapy in gastric cancer: Future directions for therapeutic targeting |
| title_fullStr | The hypoxia-inducible factor-1α in stemness and resistance to chemotherapy in gastric cancer: Future directions for therapeutic targeting |
| title_full_unstemmed | The hypoxia-inducible factor-1α in stemness and resistance to chemotherapy in gastric cancer: Future directions for therapeutic targeting |
| title_short | The hypoxia-inducible factor-1α in stemness and resistance to chemotherapy in gastric cancer: Future directions for therapeutic targeting |
| title_sort | hypoxia inducible factor 1α in stemness and resistance to chemotherapy in gastric cancer future directions for therapeutic targeting |
| topic | hypoxia-inducible factor-1α gastric cancer stemness chemoresistance deregulated signaling |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2023.1082057/full |
| work_keys_str_mv | AT gulnihalozcan thehypoxiainduciblefactor1ainstemnessandresistancetochemotherapyingastriccancerfuturedirectionsfortherapeutictargeting AT gulnihalozcan thehypoxiainduciblefactor1ainstemnessandresistancetochemotherapyingastriccancerfuturedirectionsfortherapeutictargeting AT gulnihalozcan hypoxiainduciblefactor1ainstemnessandresistancetochemotherapyingastriccancerfuturedirectionsfortherapeutictargeting AT gulnihalozcan hypoxiainduciblefactor1ainstemnessandresistancetochemotherapyingastriccancerfuturedirectionsfortherapeutictargeting |