An Overview of the Recent Development of Anticancer Agents Targeting the HIF-1 Transcription Factor

Shirai, Yukari; Chow, Christalle C T; Kambe, Gouki; Suwa, Taro; Kobayashi, Minoru; Takahashi, Itsuki; Harada, Hiroshi; Nam, Jin-Min

doi:10.3390/cancers13112813

Cited by 55 publications

(41 citation statements)

References 151 publications

(202 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, a series of PHD inhibitors and HIF-1 inhibitors are currently in clinical use for systemic diseases such as anemia (Joharapurkar et al, 2018) or for cancer therapy (Shirai et al, 2021). Despite the efficacy of this approach, demonstrated by preclinical studies, and the current availability of drugs in clinics, concerns exist regarding the HIF-1 modulation, especially in immature infants displaying ongoing developmental processes.…”

Section: New Perspectives To Counteract Rop Progressionmentioning

confidence: 99%

Decoupling Oxygen Tension From Retinal Vascularization as a New Perspective for Management of Retinopathy of Prematurity. New Opportunities From β-adrenoceptors

et al. 2022

View full text Add to dashboard Cite

Retinopathy of prematurity (ROP) is an evolutive and potentially blinding eye disease that affects preterm newborns. Unfortunately, until now no conservative therapy of active ROP with proven efficacy is available. Although ROP is a multifactorial disease, premature exposition to oxygen concentrations higher than those intrauterine, represents the initial pathogenetic trigger. The increase of oxygenation in a retina still incompletely vascularized promotes the downregulation of proangiogenic factors and finally the interruption of vascularization (ischemic phase). However, the increasing metabolic requirement of the ischemic retina induces, over the following weeks, a progressive hypoxia that specularly increases the levels of proangiogenic factors finally leading to proliferative retinopathy (proliferative phase). Considering non-modifiable the coupling between oxygen levels and vascularization, so far, neonatologists and ophthalmologists have “played defense”, meticulously searching the minimum necessary concentration of oxygen for individual newborns, refining their diagnostic ability, adopting a careful monitoring policy, ready to decisively intervene only in a very advanced stage of disease progression. However, recent advances have demonstrated the possibility to pharmacologically modulate the relationship between oxygen and vascularization, opening thus the perspective for new therapeutic or preventive opportunities. The perspective of a shift from a defensive towards an attack strategy is now at hand.

show abstract

Section: New Perspectives To Counteract Rop Progressionmentioning

confidence: 99%

Decoupling Oxygen Tension From Retinal Vascularization as a New Perspective for Management of Retinopathy of Prematurity. New Opportunities From β-adrenoceptors

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Various HIF-1α indirect inhibitors have been developed, with Rapamycin, Cetuximab, Romidepsin, and Vorinostat receiving FDA approval for the treatment of a variety of cancer types; however, as previously mentioned, no direct HIF-1α inhibitors are currently on the market [ 239 , 240 ]. Ma et al recently compiled a comprehensive review of drugs currently under investigation which indirectly inhibit HIF-1α activity, either by suppressing signaling pathways which upregulate its concentration, promoting its degradation, or by inhibiting its transcription and translation [ 241 ].…”

Section: Hypoxia and Cancer Therapymentioning

confidence: 99%

Targeting HIF-2α in the Tumor Microenvironment: Redefining the Role of HIF-2α for Solid Cancer Therapy

Davis

Recktenwald

Hutt

et al. 2022

Cancers

View full text Add to dashboard Cite

Inadequate oxygen supply, or hypoxia, is characteristic of the tumor microenvironment and correlates with poor prognosis and therapeutic resistance. Hypoxia leads to the activation of the hypoxia-inducible factor (HIF) signaling pathway and stabilization of the HIF-α subunit, driving tumor progression. The homologous alpha subunits, HIF-1α and HIF-2α, are responsible for mediating the transcription of a multitude of critical proteins that control proliferation, angiogenic signaling, metastasis, and other oncogenic factors, both differentially and sequentially regulating the hypoxic response. Post-translational modifications of HIF play a central role in its behavior as a mediator of transcription, as well as the temporal transition from HIF-1α to HIF-2α that occurs in response to chronic hypoxia. While it is evident that HIF-α is highly dynamic, HIF-2α remains vastly under-considered. HIF-2α can intensify the behaviors of the most aggressive tumors by adapting the cell to oxidative stress, thereby promoting metastasis, tissue remodeling, angiogenesis, and upregulating cancer stem cell factors. The structure, function, hypoxic response, spatiotemporal dynamics, and roles in the progression and persistence of cancer of this HIF-2α molecule and its EPAS1 gene are highlighted in this review, alongside a discussion of current therapeutics and future directions.

show abstract

“…Reliant on ATP, HSP90 is involved in activation, proper folding, assembly, transportation, conformation preservation, and breakdown of target proteins [ 46 , 47 ]. However, these target proteins encompass many elevated or transmuted carcinogenic proteins, including p53 and hTERT, some of which are associated with cancer characteristics [ 48 , 49 ]. These customer proteins in tumour generation, growth, invasion, and metastasis make HSP90 an appealing therapeutic cancer target [ 50 , 51 ].…”

Section: Overview Of Some Cancer Therapeutic Targets For Drug Discoverymentioning

confidence: 99%

Heat Shock Protein 90 (HSP90) Inhibitors as Anticancer Medicines: A Review on the Computer-Aided Drug Discovery Approaches over the Past Five Years

Magwenyane

Ugbaja

Amoako

et al. 2022

Computational and Mathematical Methods in Medicine

View full text Add to dashboard Cite

Cancer is a disease caused by the uncontrolled, abnormal growth of cells in different anatomic sites. In 2018, it was predicted that the worldwide cancer burden would rise to 18.1 million new cases and 9.6 million deaths. Anticancer compounds, often known as chemotherapeutic medicines, have gained much interest in recent cancer research. These medicines work through various biological processes in targeting cells at various stages of the cell’s life cycle. One of the most significant roadblocks to developing anticancer drugs is that traditional chemotherapy affects normal cells and cancer cells, resulting in substantial side effects. Recently, advancements in new drug development methodologies and the prediction of the targeted interatomic and intermolecular ligand interaction sites have been beneficial. This has prompted further research into developing and discovering novel chemical species as preferred therapeutic compounds against specific cancer types. Identifying new drug molecules with high selectivity and specificity for cancer is a prerequisite in the treatment and management of the disease. The overexpression of HSP90 occurs in patients with cancer, and the HSP90 triggers unstable harmful kinase functions, which enhance carcinogenesis. Therefore, the development of potent HSP90 inhibitors with high selectivity and specificity becomes very imperative. The activities of HSP90 as chaperones and cochaperones are complex due to the conformational dynamism, and this could be one of the reasons why no HSP90 drugs have made it beyond the clinical trials. Nevertheless, HSP90 modulations appear to be preferred due to the competitive inhibition of the targeted N-terminal adenosine triphosphate pocket. This study, therefore, presents an overview of the various computational models implored in the development of HSP90 inhibitors as anticancer medicines. We hereby suggest an extensive investigation of advanced computational modelling of the three different domains of HSP90 for potent, effective inhibitor design with minimal off-target effects.

show abstract

An Overview of the Recent Development of Anticancer Agents Targeting the HIF-1 Transcription Factor

Cited by 55 publications

References 151 publications

Decoupling Oxygen Tension From Retinal Vascularization as a New Perspective for Management of Retinopathy of Prematurity. New Opportunities From β-adrenoceptors

Decoupling Oxygen Tension From Retinal Vascularization as a New Perspective for Management of Retinopathy of Prematurity. New Opportunities From β-adrenoceptors

Targeting HIF-2α in the Tumor Microenvironment: Redefining the Role of HIF-2α for Solid Cancer Therapy

Heat Shock Protein 90 (HSP90) Inhibitors as Anticancer Medicines: A Review on the Computer-Aided Drug Discovery Approaches over the Past Five Years

Contact Info

Product

Resources

About