Cytochrome P450 Oxidoreductase (<i>POR</i>) Associated with Severe Paclitaxel-Induced Peripheral Neuropathy in Patients of European Ancestry from ECOG-ACRIN E5103

Shen, Fei; Jiang, Guanglong; Philips, Santosh; Gardner, Laura; Xue, Gloria; Cantor, Erica; Ly, Reynold C.; Osei, Wilberforce; Wu, Xi; Dang, Chau T.; Northfelt, Donald W.; Skaar, Todd C.; Miller, Kathy D.; Sledge, George W.; Schneider, Bryan P.

doi:10.1158/1078-0432.ccr-22-2431

Cited by 2 publications

(10 citation statements)

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“…Seven studies investigated multiple SNPs across multiple genes ( Leskelä et al, 2011 ; Bergmann et al, 2012 ; Bosó et al, 2014 ; Eckhoff et al, 2015a ; Lambrechts et al, 2015 ; Di Francia et al, 2017 ; Ciruelos et al, 2019 ). The remaining study employed genome-wide genotyping, whole-exome sequencing (WES) analyses, and TaqMan assays ( Shen et al, 2023 ). Assessing the association between CYP3A4*22 and TIPN were four studies ( de Graan et al, 2013 ; Apellaniz-Ruiz et al, 2015 ; Di Francia et al, 2017 ; Ciruelos et al, 2019 ).…”

Section: Resultsmentioning

confidence: 99%

“…Seven studies assessed the association between CYP3A5*3 and TIPN ( Leskelä et al, 2011 ; Bergmann et al, 2012 ; Hertz et al, 2012 ; Bosó et al, 2014 ; Lambrechts et al, 2015 ; Schneider et al, 2015 ; Hu et al, 2016 ). A single study assessed the association between both SNPs, CYP3A4*22 and CYP3A5*3, and TIPN ( Shen et al, 2023 ).…”

Section: Resultsmentioning

confidence: 99%

“…These studies reported ethnicity information as European or Caucasian (>95%) as described in Table 2 . One study was conducted in China ( Hu et al, 2016 ), with exclusively Chinese participants, and two in the United States ( Schneider et al, 2015 ; Shen et al, 2023 ): one of these US studies analysed patients of European ancestry ( Shen et al, 2023 ). Seven studies focussed on single cancer types: five studies on breast cancer ( Bosó et al, 2014 ; Eckhoff et al, 2015a ; Schneider et al, 2015 ; Ciruelos et al, 2019 ; Shen et al, 2023 ), and two on ovarian cancer ( Lambrechts et al, 2015 ; Hu et al, 2016 ).…”

Section: Resultsmentioning

confidence: 99%

“…One study was conducted in China ( Hu et al, 2016 ), with exclusively Chinese participants, and two in the United States ( Schneider et al, 2015 ; Shen et al, 2023 ): one of these US studies analysed patients of European ancestry ( Shen et al, 2023 ). Seven studies focussed on single cancer types: five studies on breast cancer ( Bosó et al, 2014 ; Eckhoff et al, 2015a ; Schneider et al, 2015 ; Ciruelos et al, 2019 ; Shen et al, 2023 ), and two on ovarian cancer ( Lambrechts et al, 2015 ; Hu et al, 2016 ). One study recruited both breast and ovarian cancer patients ( Apellaniz-Ruiz et al, 2015 ), and another recruited gynaecological cancers (ovarian, fallopian tube and peritoneal cancers) ( Bergmann et al, 2012 ).…”

Section: Resultsmentioning

confidence: 99%

“…Genetic factors predisposing to TIPN have been investigated, yet findings have been inconsistent and contradictory. To date, most investigations have been candidate gene studies ( Leskelä et al, 2011 ; Bergmann et al, 2012 ; de Graan et al, 2013 ; Bosó et al, 2014 ; Eckhoff et al, 2015a ; Apellaniz-Ruiz et al, 2015 ; Lambrechts et al, 2015 ; Hu et al, 2016 ; Di Francia et al, 2017 ; Ciruelos et al, 2019 ), as opposed to genome-wide association studies ( Schneider et al, 2015 ) or whole-exome sequencing (WES) analysis ( Shen et al, 2023 ). A high degree of heterogeneity has been reported in taxane pharmacokinetics (PK) ( Michael et al, 2011 ; Jabir et al, 2012 ; Hertz, 2013 ; Bosó et al, 2014 ; Sim et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

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CYP3A genetic variation and taxane-induced peripheral neuropathy: a systematic review, meta-analysis, and candidate gene study

et al. 2023

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Background: Taxane-induced peripheral neuropathy (TIPN) is an important cause of premature treatment cessation and dose-limitation in cancer therapy. It also reduces quality of life and survivorship in affected patients. Genetic polymorphisms in the CYP3A family have been investigated but the findings have been inconsistent and contradictory.Methods: A systematic review identified 12 pharmacogenetic studies investigating genetic variation in CYP3A4*22 and CYP3A5*3 and TIPN. In our candidate gene study, 288 eligible participants (211 taxane participants receiving docetaxel or paclitaxel, and 77 control participants receiving oxaliplatin) were successfully genotyped for CYP3A4*22 and CYP3A5*3. Genotyping data was transformed into a combined CYP3A metaboliser phenotype: Poor metabolisers, intermediate metabolisers and extensive metabolisers. Individual genotypes and combined CYP3A metaboliser phenotypes were assessed in relation to neurotoxicity, including by meta-analysis where possible.Results: In the systematic review, no significant association was found between CYP3A5*3 and TIPN in seven studies, with one study reporting a protective association. For CYP3A4*22, one study has reported an association with TIPN, while four other studies failed to show an association. Evaluation of our patient cohort showed that paclitaxel was found to be more neurotoxic than docetaxel (p < 0.001). Diabetes was also significantly associated with the development of TIPN. The candidate gene analysis showed no significant association between either SNP (CYP3A5*3 and CYP3A4*22) and the development of TIPN overall, or severe TIPN. Meta-analysis showed no association between these two variants and TIPN. Transformed into combined CYP3A metaboliser phenotypes, 30 taxane recipients were poor metabolisers, 159 were intermediate metabolisers, and 22 were extensive metabolisers. No significant association was observed between metaboliser status and case-control status.Summary: We have shown that the risk of peripheral neuropathy during taxane chemotherapy is greater in patients who have diabetes. CYP3A genotype or phenotype was not identified as a risk factor in either the candidate gene analysis or the systematic review/meta-analysis, although we cannot exclude the possibility of a minor contribution, which would require a larger sample size.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CYP3A genetic variation and taxane-induced peripheral neuropathy: a systematic review, meta-analysis, and candidate gene study

et al. 2023

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Harnessing Ferroptosis to Overcome Drug Resistance in Colorectal Cancer: Promising Therapeutic Approaches

Cheng,

Zhao,

et al. 2023

Cancers

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Drug resistance remains a significant challenge in the treatment of colorectal cancer (CRC). In recent years, the emerging field of ferroptosis, a unique form of regulated cell death characterized by iron-dependent lipid peroxidation, has offered new insights and potential therapeutic strategies for overcoming drug resistance in CRC. This review examines the role of ferroptosis in CRC and its impact on drug resistance. It highlights the distinctive features and advantages of ferroptosis compared to other cell death pathways, such as apoptosis and necrosis. Furthermore, the review discusses current research advances in the field, including novel treatment approaches that target ferroptosis. These approaches involve the use of ferroptosis inducers, interventions in iron metabolism and lipid peroxidation, and combination therapies to enhance the efficacy of ferroptosis. The review also explores the potential of immunotherapy in modulating ferroptosis as a therapeutic strategy. Additionally, it evaluates the strengths and limitations of targeting ferroptosis, such as its selectivity, low side effects, and potential to overcome resistance, as well as challenges related to treatment specificity and drug development. Looking to the future, this review discusses the prospects of ferroptosis-based therapies in CRC, emphasizing the importance of further research to elucidate the interaction between ferroptosis and drug resistance. It proposes future directions for more effective treatment strategies, including the development of new therapeutic approaches, combination therapies, and integration with emerging fields such as precision medicine. In conclusion, harnessing ferroptosis represents a promising avenue for overcoming drug resistance in CRC. Continued research efforts in this field are crucial for optimizing therapeutic outcomes and providing hope for CRC patients.

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Cytochrome P450 Oxidoreductase (POR) Associated with Severe Paclitaxel-Induced Peripheral Neuropathy in Patients of European Ancestry from ECOG-ACRIN E5103

Cited by 2 publications

References 35 publications

CYP3A genetic variation and taxane-induced peripheral neuropathy: a systematic review, meta-analysis, and candidate gene study

CYP3A genetic variation and taxane-induced peripheral neuropathy: a systematic review, meta-analysis, and candidate gene study

Harnessing Ferroptosis to Overcome Drug Resistance in Colorectal Cancer: Promising Therapeutic Approaches

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