Hydralazine and Enzalutamide: Synergistic Partners against Prostate Cancer

Lopes, Nair; Pacheco, Mariana Brütt; Soares-Fernandes, Diana; Correia, Margareta P.; Camilo, Vânia; Henrique, Rui; Jerónimo, Carmen

doi:10.3390/biomedicines9080976

Cited by 10 publications

(1 citation statement)

References 48 publications

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“…At least nine drugs targeting epigenetic regulators have been approved by the FDA for the treatment of hematological malignancies [ Table 2 ], and their potential for the treatment of solid cancers has been investigated in clinical trials [ 17 ]. It is noteworthy that hydralazine, previously approved for the treatment of hypertension [ 23 ], has been shown to have inhibitory properties on DNA methylation [ 24 ] and has been tested for the treatment of prostate cancer [ 25 ].…”

Section: Cancer Epigenetics and Swi/snf Chromatin Remodelersmentioning

confidence: 99%

Dysregulation of SWI/SNF Chromatin Remodelers in NSCLC: Its Influence on Cancer Therapies including Immunotherapy

Shi

Shin

2023

Biomolecules

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Lung cancer is the leading cause of cancer death worldwide. Molecularly targeted therapeutics and immunotherapy revolutionized the clinical care of NSCLC patients. However, not all NSCLC patients harbor molecular targets (e.g., mutated EGFR), and only a subset benefits from immunotherapy. Moreover, we are lacking reliable biomarkers for immunotherapy, although PD-L1 expression has been mainly used for guiding front-line therapeutic options. Alterations of the SWI/SNF chromatin remodeler occur commonly in patients with NSCLC. This subset of NSCLC tumors tends to be undifferentiated and presents high heterogeneity in histology, and it shows a dismal prognosis because of poor response to the current standard therapies. Catalytic subunits SMARCA4/A2 and DNA binding subunits ARID1A/ARID1B/ARID2 as well as PBRM1 were identified to be the most commonly mutated subunits of SWI/SNF complexes in NSCLC. Mechanistically, alteration of these SWI/SNF subunits contributes to the tumorigenesis of NSCLC through compromising the function of critical tumor suppressor genes, enhancing oncogenic activity as well as impaired DNA repair capacity related to genomic instability. Several vulnerabilities of NSCLCS with altered SWI/SNF subunits were detected and evaluated clinically using EZH2 inhibitors, PROTACs of mutual synthetic lethal paralogs of the SWI/SNF subunits as well as PARP inhibitors. The response of NSCLC tumors with an alteration of SWI/SNF to ICIs might be confounded by the coexistence of mutations in genes capable of influencing patients’ response to ICIs. High heterogenicity in the tumor with SWI/SNF deficiency might also be responsible for the seemingly conflicting results of ICI treatment of NSCLC patients with alterations of SWI/SNF. In addition, an alteration of each different SWI/SNF subunit might have a unique impact on the response of NSCLC with deficient SWI/SNF subunits. Prospective studies are required to evaluate how the alterations of the SWI/SNF in the subset of NSCLC patients impact the response to ICI treatment. Finally, it is worthwhile to point out that combining inhibitors of other chromatin modulators with ICIs has been proven to be effective for the treatment of NSCLC with deficient SWI/SNF chromatin remodelers.

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Section: Cancer Epigenetics and Swi/snf Chromatin Remodelersmentioning

confidence: 99%

Dysregulation of SWI/SNF Chromatin Remodelers in NSCLC: Its Influence on Cancer Therapies including Immunotherapy

Shi

Shin

2023

Biomolecules

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Hydralazine and Hydrazine Derivatives: Properties, Applications, and Repositioning Potential

Romão,

Siqueira,

Silva Abreu

et al. 2024

Chemistry & Biodiversity

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The investigation of new drugs is slow and costly. Drug repositioning, like with Hydralazine (HDZ), an old antihypertensive, can accelerate the process. HDZ and its hydrazonic derivatives exhibit diverse biological activities, promising for new drugs. This review explores HDZ's repositioning potential and its derivatives' applications in various biological activities. It identified 70 relevant articles through database searches. HDZ shows potential in neurology, oncology, nephrology, and gynecology, with clinical trials up to Phase III. Hydralazine‐valproate, marketed in Mexico, proves effective in combination with chemotherapy. Hydrazonic derivatives offer broad applications in medicine. Studying their structure‐activity relationship can enhance efficacy. This review summarizes their properties and pharmacological activities succinctly.

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Therapeutic applications of the prostate cancer epigenome

Cosgrave¹,

Perry²

2023

Epigenetic Cancer Therapy

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Hydralazine and Enzalutamide: Synergistic Partners against Prostate Cancer

Cited by 10 publications

References 48 publications

Dysregulation of SWI/SNF Chromatin Remodelers in NSCLC: Its Influence on Cancer Therapies including Immunotherapy

Dysregulation of SWI/SNF Chromatin Remodelers in NSCLC: Its Influence on Cancer Therapies including Immunotherapy

Hydralazine and Hydrazine Derivatives: Properties, Applications, and Repositioning Potential

Therapeutic applications of the prostate cancer epigenome

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