&lt;b&gt;&lt;i&gt;Topoisomerase 1&lt;/i&gt;&lt;/b&gt; Promoter Variants and Benefit from Irinotecan in Metastatic Colorectal Cancer Patients

Paolicchi, Elisa; Vivaldi, Caterina; Gregorio, Veronica De; Crea, Francesco; Fornaro, Lorenzo; Masi, Gianluca; Loupakis, Fotios; Graziano, Francesco; Ronzoni, Monica; Ricci, Vincenzo; Falcone, Alfredo; Danesi, Romano

doi:10.1159/000448004

Cited by 6 publications

(4 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Some researches explored the relationship between SNPs of other genes and clinical benefit of irinotecan-based therapy, such as TOP 1, SLCO1B1, ABCC2, and UGT1A1. 23 , 24 Although the function of these genes mentioned above mainly take part in drug-metabolizing pathway in vivo, mechanisms affecting the clinical efficacy of irinotecan-based therapy were different from MLH1 rs1800734 SNPs in our study.…”

Section: Discussioncontrasting

confidence: 65%

Association of MLH1 single nucleotide polymorphisms with clinical outcomes of first-line irinotecan-based chemotherapy in colorectal cancer

Wang

Zhang

et al. 2018

OTT

View full text Add to dashboard Cite

PurposeSeveral studies have proved that single nucleotide polymorphisms (SNPs) of mismatch repair system genes are closely related to the development of colorectal cancer (CRC) by causing microsatellite instability, while effects of the SNPs of MMR system-related genes on the clinical outcomes of cytotoxic chemotherapy are less understood. The aim of this study explored the influence of MLH1 SNPs on clinical outcomes of first-line irinotecan-based chemotherapy in CRC.Patients and methodsA total of 125 metastatic colorectal cancer (mCRC) patients who received first-line irinotecan-based chemotherapy (none of them combined with bevacizumab or cetuximab) were enrolled in this study. Blood samples or formalin-fixed paraffin-embedded tissues of study population were taken. DNA isolation and genotyping analyzed were obtained for potential functional polymorphisms of MLH1 rs1800734 by real-time PCR. Progression-free survival (PFS) was the primary endpoint and tumor response rate (RR) was the secondary endpoint of this study.ResultsOf all the assessable population, the result showed no statistical difference among the three types SNPs of MLH1 rs1800734 (AA, AG, GG) for RR (P=0.859), and also without significant difference for AA + AG combined variants vs GG variant (P=0.849). The median PFS for AA, AG, and GG variants of MLH1 rs1800734 SNPs were 9.4 months, 7.0 months, and 6.9 months, respectively (log-rank P=0.031). Interestingly, compared with AA variant of MLH1 rs1800734 SNPs, GG variant showed a shorter PFS (HR: 3.49; 95 CI: 1.02–11.94; P=0.046). Furthermore, the median PFS of AA + AG combined variants and GG variant were 8.3 months and 6.9 months (log-rank P=0.037), and GG variant have a decreased trend with no significant difference (HR: 1.57; 95 CI: 0.98–2.53; P=0.061).ConclusionThe AA variant of MLH1 rs1800734 SNPs has a longer PFS in first-line irinotecan-based chemotherapy for mCRC patients, and the result needs to be further confirmed by prospective studies in the future.

show abstract

Section: Discussioncontrasting

confidence: 65%

Association of MLH1 single nucleotide polymorphisms with clinical outcomes of first-line irinotecan-based chemotherapy in colorectal cancer

Wang

Zhang

et al. 2018

OTT

View full text Add to dashboard Cite

show abstract

“…It is an essential nuclear enzyme involved in DNA replication, transcription, translation, recombination and repair. Paolicchi analyzed two SNPs of Topoisomerase 1 (topo-1) gene including rs6072249 and rs34282819 to find the benefit from irinotecan in mCRC patients, but they find no correlation with clinical parameters (OS and PFS) (Paolicchi, Vivaldi et al 2016)…”

Section: Ugt and Top1mentioning

confidence: 99%

Pharmacogenetics of Anticancer Drug Sensitivity and Toxicity in Colorectal Cancer

Moradi‐Marjaneh

Khazaei

Seifi

et al. 2018

CPD

View full text Add to dashboard Cite

Inter-individual differences in drug response are an important cause of failure in anticancer treatment and adverse drug events in cancer patients. Gene polymorphisms related to these outcomes have been investigated in an effort to find new genetic biomarkers to predict toxicity and response to anticancer drugs. Evaluating the value single nucleotide polymorphisms (SNPs) in the genes involved in transportation, activation and metabolism of anticancer drugs provides a promising approach to select the appropriate therapeutic regimes with at least adverse reactions. This review summarizes the current knowledge about the relationship between of SNPs involved in the transportation, activation and metabolism of anticancer drugs and treatment outcomes in colorectal cancer (CRC) patients.

show abstract

“…No single genotype was found to predict the clinical outcomes (response rate, progression-free survival and overall survival). Further, well planned pharmacogenetic studies are required to detect predictive markers to irinotecan therapy [32].…”

Section: Drug Targetsmentioning

confidence: 99%

Single Nucleotide Polymorphisms as Biomarkers for Drug Response and Toxicity in the Management of Colorectal Cancer

Varma¹,

Mathaiyan²,

Shewade³

2018

J Pharmacogenomics Pharmacoproteom

View full text Add to dashboard Cite

The current methods of cancer treatment don't focus on the influence of interpatient genetic variations on the treatment outcomes. Genetic variations in the genes which are involved with drug metabolism and targets can affect treatment response and toxicity. In the recent time, many advances have been made to detect such candidate gene variations and use them as biomarkers in predicting the treatment outcomes in colorectal cancer (CRC). CRC remains one of the common causes of worldwide morbidity and mortality. In the last decade, many drugs have been approved including targeted therapies for the management of CRC which lead to improvement in the median survival and overall survival rate. However, there are significant variations in the response rate and toxicity among CRC patients with the current anti-cancer drugs. Interindividual response variations to chemotherapy can be influenced by several factors among them the genetic factor plays a key role. This emphasizes the need for the new genetic biomarkers which enable the selection of optimal drugs to benefit the patient care. This review focuses on single nucleotide polymorphisms which are known to affect the outcome of anticancer drugs used in the management of colorectal cancer.

show abstract

<b><i>Topoisomerase 1</i></b> Promoter Variants and Benefit from Irinotecan in Metastatic Colorectal Cancer Patients

Cited by 6 publications

References 21 publications

Association of MLH1 single nucleotide polymorphisms with clinical outcomes of first-line irinotecan-based chemotherapy in colorectal cancer

Association of MLH1 single nucleotide polymorphisms with clinical outcomes of first-line irinotecan-based chemotherapy in colorectal cancer

Pharmacogenetics of Anticancer Drug Sensitivity and Toxicity in Colorectal Cancer

Single Nucleotide Polymorphisms as Biomarkers for Drug Response and Toxicity in the Management of Colorectal Cancer

Contact Info

Product

Resources

About