CYP1A1 genetic polymorphism is a promising predictor to improve chemotherapy effects in patients with metastatic breast cancer treated with docetaxel plus thiotepa vs. docetaxel plus capecitabine

Zhou, Xinna; Wang, Xiaoli; Song, Qingkun; Morse, Michael A.; Hobeika, Amy; Gwin, William R.; Ren, Jun; Lyerly, H. Kim

doi:10.1007/s00280-017-3500-9

Cited by 8 publications

(4 citation statements)

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“…Nie et al previously reported that the polymorphism of CYP1A1 has a linkage with clinical outcome of NSCLC patients treated with EGFR-TKI (Nie et al, 2011a;Nie et al, 2011b). Previous study also showed that CYP1A1 genetic polymorphism was a promising predictor to improve chemotherapy effects in patients with metastatic breast cancer (Zhou et al, 2018).…”

Section: Discussionmentioning

confidence: 91%

Polymorphisms of Drug-Metabolizing Enzymes and Transporters Contribute to the Individual Variations of Erlotinib Steady State Trough Concentration, Treatment Outcomes, and Adverse Reactions in Epidermal Growth Factor Receptor–Mutated Non-Small Cell Lung Cancer Patients

et al. 2020

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Background: Erlotinib is presently the first line treatment for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) active mutation. An increasing number of evidences show that the treatment efficacy and toxicities are considerably heterogeneous among individuals. Hence, it is necessary to find biological predictors for further individualized treatment of erlotinib in NSCLC patients.Methods: Our present study enrolled 87 cases of NSCLC patients who had been administrated erlotinib with a fixed dose (150 mg/d). Eleven polymorphisms in seven genes of drug-metabolizing enzymes and transporters were genotyped and the steady state trough concentrations were also determined.Results: There were significant variances in the steady-state erlotinib trough plasma concentrations, ranging from 315.6 ng/ml to 4479.83 ng/ml. Erlotinib steady state trough concentration was remarkably lower in current smoking patients. The steady state trough concentration of GG in rs1048943 of CYP1A1 was significantly higher than that of AA allele carriers. The polymorphism of CYP1A2 was significantly associated with the severity of skin rash, and the development of diarrhea was associated with SNPs in ABCB1 and CYP3A5. We also observed that GG allele in CYP1A1 was accompanied with a longer PFS in our study. Conclusion:A large variability of erlotinib steady state trough concentration was found among Chinese Han population. SNPs in CYP1A1 appeared to influence the steady state

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Section: Discussionmentioning

confidence: 91%

Polymorphisms of Drug-Metabolizing Enzymes and Transporters Contribute to the Individual Variations of Erlotinib Steady State Trough Concentration, Treatment Outcomes, and Adverse Reactions in Epidermal Growth Factor Receptor–Mutated Non-Small Cell Lung Cancer Patients

et al. 2020

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“…Fourth, the associations observed in this study pertain to docetaxel administered in combination with cyclophosphamide and sometimes epirubicin, and not docetaxel monotherapy. Fifth, some SNPs were singled out based on findings from earlier studies that used other combinations of taxane-based chemotherapy [ 15 , 35 , 51 – 56 ]. As our study was based on routine clinical care data, our findings warrant confirmation in randomized clinical trials before genotyping can be used to guide taxane effectiveness in routine clinical practice.…”

Section: Discussionmentioning

confidence: 99%

Single-nucleotide polymorphisms and the effectiveness of taxane-based chemotherapy in premenopausal breast cancer: a population-based cohort study in Denmark

Hjorth

Damkier

Stage

et al. 2022

Breast Cancer Res Treat

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Purpose Taxane-based chemotherapy is the primary treatment for premenopausal breast cancer. Although being inconsistent, research suggests that variant alleles alter pharmacokinetics through reduced function of OATP transporters (limiting hepatic uptake), CYP-450 enzymes (hampering drug metabolism), and ABC transporters (decreasing clearance). Reduced function of DNA repair enzymes may hamper effectiveness through dose-limiting toxicities. We investigated whether single-nucleotide polymorphisms (SNPs) were associated with breast cancer recurrence or mortality in premenopausal women diagnosed with breast cancer. Methods We conducted a population-based cohort study of premenopausal women diagnosed with non-distant metastatic breast cancer in Denmark during 2007‒2011, when guidelines recommended adjuvant combination chemotherapy (taxanes, anthracyclines, and cyclophosphamide). Using archived formalin-fixed paraffin-embedded primary tumor tissue, we genotyped 26 SNPs using TaqMan assays. Danish health registries provided data on breast cancer recurrence (through September 25, 2017) and death (through December 31, 2019). We fit Cox regression models to calculate crude hazard ratios (HRs) and 95% confidence intervals (CIs) for recurrence and mortality across genotypes. Results Among 2,262 women, 249 experienced recurrence (cumulative incidence: 13%) and 259 died (cumulative incidence: 16%) during follow-up (median 7.0 and 10.1 years, respectively). Mortality was increased in variant carriers of GSTP1 rs1138272 (HR: 1.30, 95% CI 0.95–1.78) and CYP3A rs10273424 (HR: 1.33, 95% CI 0.98–1.81). SLCO1B1 rs2306283 (encoding OATP1B1) variant carriers had decreased recurrence (HR: 0.82, 95% CI 0.64–1.07) and mortality (HR: 0.77, 95% CI 0.60–0.98). Conclusion Docetaxel effectiveness was influenced by SNPs in GSTP1, CYP3A, and SLCO1B1 in premenopausal women with non-distant metastatic breast cancer, likely related to altered docetaxel pharmacokinetics. These SNPs may help determine individual benefit from taxane-based chemotherapy.

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“…Several studies have shown that polymorphisms in drug-metabolising genes not only pose as a risk factor for malignancy but also can serve as a predictive marker for drug efficacy and targeted therapies [27,28]. In metastatic breast cancer, patients with the CYP1A1*2C gene variant responded better to a treatment regimen involving docetaxel and capecitabine compared to those with the homozygous wildtype (CYP1A1*1) genotype (AA) who experienced a better efficacy with a combination of docetaxel with thiotepa [29]. In early breast cancer, CYP1A2 rs762551 has been shown to be a potential predictive marker for patients treated with aromatase inhibitors paving the way towards individualised tailored assessment of therapy [30].…”

Section: Cyp1a1/a2mentioning

confidence: 99%

“…Prodrugs that are bioactivated by CYP1 enzymes can broadly be classified into four groups of agents and include flavonoids, benzothiazoles, stilbenes and alkylating agents [29]. Aminoflavone (NSC686288, Figure 3), a ligand of AhR, has been shown to selectively induce apoptosis in MCF-7 breast cancer cells by activating the transcription of CYP1A1 and CYP1B1 with functional activity confirmed using the ethoxyresorufin-O-deethylase (EROD) activity assay both in vitro and in xenograft models [31].…”

Section: Cyp1a1/a2mentioning

confidence: 99%

Intratumoural Cytochrome P450 Expression in Breast Cancer: Impact on Standard of Care Treatment and New Efforts to Develop Tumour-Selective Therapies

Sneha

Baker

Green³

et al. 2021

Biomedicines

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Despite significant advances in treatment strategies over the past decade, selective treatment of breast cancer with limited side-effects still remains a great challenge. The cytochrome P450 (CYP) family of enzymes contribute to cancer cell proliferation, cell signaling and drug metabolism with implications for treatment outcomes. A clearer understanding of CYP expression is important in the pathogenesis of breast cancer as several isoforms play critical roles in metabolising steroid hormones and xenobiotics that contribute to the genesis of breast cancer. The purpose of this review is to provide an update on how the presence of CYPs impacts on standard of care (SoC) drugs used to treat breast cancer as well as discuss opportunities to exploit CYP expression for therapeutic intervention. Finally, we provide our thoughts on future work in CYP research with the aim of supporting ongoing efforts to develop drugs with improved therapeutic index for patient benefit.

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CYP1A1 genetic polymorphism is a promising predictor to improve chemotherapy effects in patients with metastatic breast cancer treated with docetaxel plus thiotepa vs. docetaxel plus capecitabine

Abstract: Overall, DT and DC result in similar clinical efficacy for MBC patients; however, efficacy for each therapy differs depending on CYP1A1*2C genotype.

Cited by 8 publications

References 35 publications

Polymorphisms of Drug-Metabolizing Enzymes and Transporters Contribute to the Individual Variations of Erlotinib Steady State Trough Concentration, Treatment Outcomes, and Adverse Reactions in Epidermal Growth Factor Receptor–Mutated Non-Small Cell Lung Cancer Patients

Polymorphisms of Drug-Metabolizing Enzymes and Transporters Contribute to the Individual Variations of Erlotinib Steady State Trough Concentration, Treatment Outcomes, and Adverse Reactions in Epidermal Growth Factor Receptor–Mutated Non-Small Cell Lung Cancer Patients

Single-nucleotide polymorphisms and the effectiveness of taxane-based chemotherapy in premenopausal breast cancer: a population-based cohort study in Denmark

Intratumoural Cytochrome P450 Expression in Breast Cancer: Impact on Standard of Care Treatment and New Efforts to Develop Tumour-Selective Therapies

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