Polymorphisms of ABCB1, CYP3A4 and CYP3A5 Genes in Ovarian Cancer and Treatment Response in Poles

Fiszer-Maliszewska, Ł; Łaczmański, Łukasz; Dolinska, Aneta; Jagas, Maria; Kołodziejska, Ewelina; Jankowska, Magdalena; Kuśnierczyk, Piotr

doi:10.21873/anticanres.12370

Cited by 7 publications

(11 citation statements)

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“…Patients carrying CYP3A5*3/*1 genotypes had a significant association Additionally, reports have shown that the CYP3A4 rs2740574 variant is inversely associated with ovarian cancer morbidity [91,92]. These data contradict earlier studies indicating the absence of an association between the CYP3A4 rs2740574 variant and ovarian cancer risk [93,94]. Other CYP3A4 genetic variants had no impact on ovarian cancer susceptibility [94].…”

Section: Impact Of Cyp Polymorphisms On Chemotherapeutic Agent Metabo...mentioning

confidence: 87%

“…In contrast, the CYP3A4*16 genetic allele did not affect paclitaxel pharmacokinetics or metabolism [107]. Despite the strong structural similarity (85% homology) between CYP3A4 and CYP3A5, CYP3A5 polymorphisms had no association with overall survival, patient outcomes, or chemotherapy toxicity in ovarian cancer patients treated with platinum and taxane drugs [51,94,105].…”

Section: Impact Of Cyp Polymorphisms On Chemotherapeutic Agent Metabo...mentioning

confidence: 97%

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Targeting Cytochrome P450 Enzymes in Ovarian Cancers: New Approaches to Tumor-Selective Intervention

Al-saraireh,

Alshammari,

Abu-azzam

et al. 2023

Biomedicines

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Over the past decade, there have been significant developments in treatment for ovarian cancer, yet the lack of targeted therapy with few side effects still represents a major issue. The cytochrome P450 (CYP) enzyme family plays a vital role in the tumorigenesis process and metabolism of drugs and has a negative impact on therapy outcomes. Gaining more insight into CYP expression is crucial to understanding the pathophysiology of ovarian cancer since many isoforms are essential to the metabolism of xenobiotics and steroid hormones, which drive the disease’s development. To the best of our knowledge, no review articles have documented the intratumoral expression of CYPs and their implications in ovarian cancer. Therefore, the purpose of this review is to provide a clear understanding of differential CYP expression in ovarian cancer and its implications for the prognosis of ovarian cancer patients, together with the effects of CYP polymorphisms on chemotherapy metabolism. Finally, we discuss opportunities to exploit metabolic CYP expression for the development of novel therapeutic methods to treat ovarian cancer.

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Section: Impact Of Cyp Polymorphisms On Chemotherapeutic Agent Metabo...mentioning

confidence: 87%

Section: Impact Of Cyp Polymorphisms On Chemotherapeutic Agent Metabo...mentioning

confidence: 97%

Targeting Cytochrome P450 Enzymes in Ovarian Cancers: New Approaches to Tumor-Selective Intervention

Al-saraireh,

Alshammari,

Abu-azzam

et al. 2023

Biomedicines

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show abstract

“…On the other hand, an increase in the level of CYP3A5 expression is observed in ovarian, colorectal, and breast cancers (27)(28)(29). A recent study has shown that there is no association between the CYP3A5*3 genotype and risk of ovarian cancer (30), indicating that the level of CYP3A5 expression does not seem to affect some cancers, such as ovarian cancer. In RCC, the level of CYP3A5 expression was down-regulated in most cancer tissues as well as in liver and lung cancer tissues.…”

Section: Discussionmentioning

confidence: 99%

Relevance of CYP3A5 Expression on the Clinical Outcome of Patients With Renal Cell Carcinoma

Matsumoto

Watari

et al. 2021

Anticancer Res

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Background/Aim: This study aimed to elucidate the detailed characteristics of CYP3A5 expression and the association between CYP3A5 expression and clinical outcomes in patients with renal cell carcinoma (RCC).Patients and Methods: This study retrospectively enrolled 124 Japanese patients with RCC treated at the Okayama University Hospital. The commonest CYP3A5 gene polymorphism, CYP3A5*3, and expression levels of CYP3A5 mRNA and protein in each tissue were examined. Results: Expression of CYP3A5 mRNA and protein in RCC tissues was significantly down-regulated compared to that in adjacent normal tissues. High level of CYP3A5 mRNA expression significantly extended cancer-specific survival (p=0.004) and overall survival (p=0.002). The CYP3A5 mRNA expression level was identified as a significant independent prognostic factor for both cancer-specific survival and overall survival. Conclusion: CYP3A5 could serve as a potential marker for prognostication and treatment planning for patients with RCC.Renal cell carcinoma (RCC) is the commonest cancer of the kidney and comprises approximately 90% of all cases of kidney cancer (1). RCC is estimated to account for 2% of new cancer cases or cancer deaths worldwide (2, 3). Advances in cancer therapy have improved the 5-year survival rates for RCC, although the overall prognosis for RCC remains unsatisfactory, at approximately 65% of the current 5-year survival rates for RCC (4). Moreover, the global incidence of RCC has been gradually increasing (5).Cytochrome P450 (CYP) 3A is the most abundant CYP subfamily that is responsible for the metabolism of a large number of substrates in humans. The major CYP3A isoform is CYP3A4; however, three minor isoforms, CYP3A5, CYP3A7, and CYP3A43, have been reported (6). Of these, CYP3A5 is the most abundantly expressed enzyme of the minor CYP3A isoforms in adults (6). The CYP3A5 gene is highly polymorphic, which causes individual variations in the expression of CYP3A5. The commonest allele responsible for the variable protein expression of CYP3A5 is CYP3A5*3 (rs776746, 6986 A>G) (7). Individuals who are homozygous for the CYP3A5*3 allele either express very low levels of CYP3A5 protein or lack CYP3A5 protein expression (7,8). Interestingly, evidence from small cohort studies indicate that CYP3A5, but not CYP3A4, is markedly expressed in the normal kidney with a CYP3A5*1 allele (9, 10). Thus, CYP3A5 is considered to play a role in substrate metabolism in the kidney.Most studies on the role of CYP3A5 in cancer have focused on the metabolism of exogenous agents, such as anticancer drugs, in the liver and small intestine. Many anticancer drugs are reported to be candidate substrates of CYP3A5 (11,12). In addition, evidence has shown that CYP3A5 has several roles in cancer progression, via the metabolism of endogenous or carcinogenic substrates, that are independent of the metabolism of anticancer drugs (13).

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“…APOA4 was reported to be closely related to urinary bladder cancer (Soukup et al 2019). CYP3A4 is currently indicated for the treatment of ovarian and breast cancer (Fiszer-Maliszewska et al 2018;Liu et al 2019). Bian et al found that GCG affected the development and progression of colon cancer (Bian et al 2019).…”

Section: Discussion：mentioning

confidence: 99%

Peer Review #1 of "Identification of DEGs and transcription factors involved in H. pylori-associated inflammation and their relevance with gastric cancer (v0.1)"

2020

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Background: Previous studies have indicated that chronic inflammation linked to H. pylori infection is the leading causes for gastric cancer (GC). However, the exact mechanism is not entirely clear until now. Purpose: To identify the key molecules and TFs involved in H. pylori infection and to provide new insights into H. pylori-associated carcinogenesis and lay the groundwork for the prevention of GC. Results: GO and KEGG analysis revealed that the DEGs of Hp +-NAG were mainly associated with the immune response, chemokine activity, extracellular region and rheumatoid arthritis pathway. The DEGs of Hp +-AG-IM were related to the apical plasma membrane, intestinal cholesterol absorption, transporter activity and fat digestion and absorption pathway. In Hp +-NAG network, the expression of TNF, CXCL8, MMP9, CXCL9, CXCL1, CCL20, CTLA4, CXCL2, C3, SAA1 and FOXP3, JUN had statistical significance between normal and cancer in TCGA database. In Hp +-AG-IM network the expression of APOA4, GCG, CYP3A4, XPNPEP2 and FOXP3, JUN were statistically different in the comparison of normal and cancer in TCGA database. FOXP3 were negatively associated with overall survival, and the association for JUN was positive. Conclusion: The current study identified key DEGs and their transcriptional regulatory networks involved in H. pylori-associated NAG, AG-IM and GC and found that patients with higher expressed FOXP3 or lower expressed JUN had shorter overall survival time. Our study provided new directions for inflammationassociated oncogenic transformation involved in H. pylori infection.

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Polymorphisms of ABCB1, CYP3A4 and CYP3A5 Genes in Ovarian Cancer and Treatment Response in Poles

Abstract: These findings may contribute to a better prediction of therapy outcome.

Cited by 7 publications

References 0 publications

Targeting Cytochrome P450 Enzymes in Ovarian Cancers: New Approaches to Tumor-Selective Intervention

Targeting Cytochrome P450 Enzymes in Ovarian Cancers: New Approaches to Tumor-Selective Intervention

Relevance of CYP3A5 Expression on the Clinical Outcome of Patients With Renal Cell Carcinoma

Peer Review #1 of "Identification of DEGs and transcription factors involved in H. pylori-associated inflammation and their relevance with gastric cancer (v0.1)"

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