The hypoxia-inducible factor-1α in stemness and resistance to chemotherapy in gastric cancer: Future directions for therapeutic targeting

Abstract

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.

Network pharmacology and experimental evaluation strategies to decipher the underlying pharmacological mechanism of Traditional Chinese Medicine CFF-1 against prostate cancer

“…Overexpression of HIF-1α, a key component of this pathway, has been associated with poor prognoses in PCa patients [ 29 ]. Consequently, inhibiting HIF-1, as indicated by our study’s results, may provide therapeutic benefits, corroborating findings from previous genetic and pharmacological studies [ 30 – 32 ]. IL-6, a major inflammatory factor within the tumor microenvironment, is intricately involved in tumor progression, immune modulation, and inflammatory responses [ 33 ].…”

YTHDF2 promotes gastric cancer progression and enhances chemoradiotherapy resistance

“…The mounting evidence suggests that hypoxia plays a crucial role as a driving force for the progression of GC (Li et al, 2022;Lin et al, 2022;Ozcan, 2023;Xing et al, 2021). HIF-1α, a component of HIF-1, acts as a central controller governing the cellular and overall physiological adaptation to low oxygen levels (45)(46)(47)(48).…”

Chemotherapy Resistance in Cancer: Mechanism and Roadmap to Evade Exploring Apoptosis

“…The crisis is more pronounced in low and middle-income countries due to the inaccessibility of quality diagnostic and treatment measures (Walker et al, 2021). Gathering the shreds of evidence so far, it is understood cancer cells exhibit chemo resistance via a multitude of mechanisms, which can be generally classified into intrinsic and acquired (Cadamuroet al, 2017;Comandatoreet al, 2022;Hu & Chen, 2021;Luoet al, 2023;Ozcan, 2023;Palamariset al, 2021;Ren & Yu, 2018;Tuneet al, 2022;Wanget al, 2022;Yeldaget al, 2018;Zhu et al, 2023).…”