A potentiated cooperation of carbonic anhydrase IX and histone deacetylase inhibitors against cancer

Ruzzolini, Jessica; Laurenzana, Anna; Andreucci, Elena; Peppicelli, Silvia; Bianchini, Francesca; Carta, Fabrizio; Supuran, Claudiu T.; Romanelli, Maria Novella; Nediani, Chiara; Calorini, Lido

doi:10.1080/14756366.2019.1706090

Cited by 22 publications

(19 citation statements)

References 52 publications

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“…The glycoprotein CA9 has been studied in the recent years, whereby the expression was higher in wide spectrum of malignancy and showed the potential for cancer therapy [30][31][32]. Served as the mediator of intracellular pH that seldom present in the normal human cells, this zinc-containing enzyme may maintain the tumor proliferation in a hypoxic microenvironment and contribute to the tumor invasiveness as well as therapeutic resistance according to previous studies [19,[33][34][35].…”

Section: Discussionmentioning

confidence: 97%

Association of Carbonic Anhydrase 9 Polymorphism and the Epithelial Growth Factor Receptor Mutations in Lung Adenocarcinoma Patients

Chiou

Tsao

et al. 2020

Diagnostics

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Carbonic anhydrase 9 (CA9) plays a vital role in lung cancer progression. The current study explored the effect of CA9 gene polymorphisms and the epidermal growth factor receptor (EGFR) mutations on the clinicopathological characters of lung adenocarcinoma. In this study, three loci of CA9 single nucleotide polymorphism (SNP) (rs2071676 A > G, rs3829078 A > G, and rs1048638 C > A) were genotyped using the TaqMan allelic discrimination method in 193 EGFR wild type individuals and 281 EGFR mutation subjects. After adjusting for age, gender, and cigarette smoking status in logistic regression, all three CA9 SNPs illustrated a non-significant difference for the distribution between the EGFR wild type group and EGFR mutation group. Nevertheless, a significantly lower rate of CA9 SNP rs2071676 AG (adjusted odds ratio (AOR): 0.40, 95% confidence interval (CI): 0.16–0.95, p = 0.039) and AG + GG (AOR: 0.43, 95% CI: 0.18–0.98, p = 0.046) were found in the male population with L858R EGFR mutation compared to men with EGFR wild type. In addition, the CA9 SNP rs2071676 AG + GG genotype were significantly correlated to the lower tumor stage of lung adenocarcinoma in the whole study population (p = 0.044) and EGFR wild type individuals (p = 0.033). For the male population, the presence of CA9 SNP rs2071676 AG + GG genotype was also correlated to a lower tumor stage (p = 0.037) and fewer lymph node invasion (p = 0.003) in those with EGFR wild type. In conclusion, the existence of CA9 SNP rs2071676 is associated with the rate of EGFR L858R mutation in males. Furthermore, the CA9 SNP rs2071676 is correlated to lower tumor stage and lower risk for developing lymph node metastasis in lung adenocarcinoma, mainly in the EGFR wild type.

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Section: Discussionmentioning

confidence: 97%

Association of Carbonic Anhydrase 9 Polymorphism and the Epithelial Growth Factor Receptor Mutations in Lung Adenocarcinoma Patients

Chiou

Tsao

et al. 2020

Diagnostics

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“…Ruzzolini and coworkers recently investigated the joint in vitro antiproliferative action of suberoylanilide hydroxamic acid (SAHA), the first FDA-approved HDAC inhibitor, and SLC-0111 (Figure 18) [89,90]. The SLC-0111+SAHA combination exhibited enhanced antiproliferative effects against HCT116 colorectal carcinoma, MCF7 breast carcinoma, and A375M6 melanoma cell lines.…”

Section: Scl-0111 and Suberoylanilide Hydroxamic Acidmentioning

confidence: 99%

Carbonic Anhydrase IX Inhibitors as Candidates for Combination Therapy of Solid Tumors

Kalinin

Malkova

Sharonova

et al. 2021

IJMS

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Combination therapy is becoming imperative for the treatment of many cancers, as it provides a higher chance of avoiding drug resistance and tumor recurrence. Among the resistance-conferring factors, the tumor microenvironment plays a major role, and therefore, represents a viable target for adjuvant therapeutic agents. Thus, hypoxia and extracellular acidosis are known to select for the most aggressive and resilient phenotypes and build poorly responsive regions of the tumor mass. Carbonic anhydrase (CA, EC 4.2.1.1) IX isoform is a surficial zinc metalloenzyme that is proven to play a central role in regulating intra and extracellular pH, as well as modulating invasion and metastasis processes. With its strong association and distribution in various tumor tissues and well-known druggability, this protein holds great promise as a target to pharmacologically interfere with the tumor microenvironment by using drug combination regimens. In the present review, we summarized recent publications revealing the potential of CA IX inhibitors to intensify cancer chemotherapy and overcome drug resistance in preclinical settings.

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“…Besides the histone alterations, HDACs can remove acetyl unit also from non-histone proteins, including estrogen receptors, transcription factors, and chaperons. In this sense, it interferes with several DNA processes, such as protein stability and DNA binding activity [ 36 ]. Considering that the overexpression or abnormal recruitment of HDACs are the most frequent epigenetic alterations in tumor onset and progression, inhibition of HDACs has been considered a promising strategy to fight cancer spread [ 37 ].…”

Section: Enzyme Interactionsmentioning

confidence: 99%

Groundbreaking Anticancer Activity of Highly Diversified Oxadiazole Scaffolds

Benassi

Doria

Pirota

2020

IJMS

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Nowadays, an increasing number of heterocyclic-based drugs found application in medicinal chemistry and, in particular, as anticancer agents. In this context, oxadiazoles—five-membered aromatic rings—emerged for their interesting biological properties. Modification of oxadiazole scaffolds represents a valid strategy to increase their anticancer activity, especially on 1,2,4 and 1,3,4 regioisomers. In the last years, an increasing number of oxadiazole derivatives, with remarkable cytotoxicity for several tumor lines, were identified. Structural modifications, that ensure higher cytotoxicity towards malignant cells, represent a solid starting point in the development of novel oxadiazole-based drugs. To increase the specificity of this strategy, outstanding oxadiazole scaffolds have been designed to selectively interact with biological targets, including enzymes, globular proteins, and nucleic acids, showing more promising antitumor effects. In the present work, we aim to provide a comprehensive overview of the anticancer activity of these heterocycles, describing their effect on different targets and highlighting how their structural versatility has been exploited to modulate their biological properties.

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A potentiated cooperation of carbonic anhydrase IX and histone deacetylase inhibitors against cancer

Cited by 22 publications

References 52 publications

Association of Carbonic Anhydrase 9 Polymorphism and the Epithelial Growth Factor Receptor Mutations in Lung Adenocarcinoma Patients

Association of Carbonic Anhydrase 9 Polymorphism and the Epithelial Growth Factor Receptor Mutations in Lung Adenocarcinoma Patients

Carbonic Anhydrase IX Inhibitors as Candidates for Combination Therapy of Solid Tumors

Groundbreaking Anticancer Activity of Highly Diversified Oxadiazole Scaffolds

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