Reproducibility of pharmacogenetics findings for paclitaxel in a heterogeneous population of patients with lung cancer

PloS One
T M SissungW D Figg

Abstract

Pharmacogenetics studies have identified several allelic variants with the potential to reduce toxicity and improve treatment outcome. The present study was designed to determine if such findings are reproducible in a heterogenous population of patients with lung cancer undergoing therapy with paclitaxel. We designed a prospective multi-institutional study that recruited n = 103 patients receiving paclitaxel therapy with a 5-year follow up. All patients were genotyped using the Drug Metabolizing Enzymes and Transporters (DMET) platform, which ascertains 1931 genotypes in 235 genes. Progression-free survival (PFS) of paclitaxel therapy and clinically-significant paclitaxel toxicities were classified and compared according to genotype. Initial screening revealed eleven variants that are associated with PFS. Of these, seven variants in ABCB11 (rs4148768), ABCC3 (rs1051640), ABCG1 (rs1541290), CYP8B1 (rs735320), NR3C1 (rs6169), FMO6P (rs7889839), and GSTM3 (rs7483) were associated with paclitaxel PFS in a multivariate analysis accounting for clinical covariates. Multivariate analysis revealed four SNPs in VKORC1 (rs2884737), SLC22A14 (rs4679028), GSTA2 (rs6577), and DCK (rs4643786) were associated with paclitaxel toxicities. With t...Continue Reading

References

Jul 31, 2001·International Journal of Cancer. Journal International Du Cancer·T OguriN Kohno
Feb 11, 2003·American Journal of Physiology. Gastrointestinal and Liver Physiology·John Y L Chiang
Aug 24, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Wim J E TissingRob Pieters
Oct 8, 2005·Cancer Biology & Therapy·Nicola F SmithAlex Sparreboom
Apr 17, 2007·British Journal of Pharmacology·S Teng, M Piquette-Miller
Sep 8, 2007·American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists·Lisa A Kroon
Sep 15, 2007·The Journal of Pharmacology and Experimental Therapeutics·Jatinder K LambaRaul Ribeiro
Jun 9, 2009·Journal of Experimental & Clinical Cancer Research : CR·Stacy S Shord, Shitalben R Patel
Dec 19, 2009·Pharmacogenomics·Tristan M SissungJohn F Deeken
Mar 11, 2010·Current Drug Metabolism·Xin-Sheng LaiShu-Feng Zhou
May 9, 2012·Cancer Chemotherapy and Pharmacology·Toshitaka UchiyamaKayoko Saito
Feb 28, 2013·International Journal of Molecular Sciences·Consolación MelguizoAntonia Aranega
Apr 17, 2013·Clinical Pharmacology and Therapeutics·K PussegodaUNKNOWN CPNDS Consortium
Aug 7, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Anne-Joy M de GraanRon H J Mathijssen
Oct 22, 2013·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Radosław JanuchowskiMaciej Zabel
Nov 2, 2013·Scientific Reports·Yanbin ZhaoLi Cai
Mar 19, 2014·Anti-cancer Drugs·Vincent A de WegerJan H M Schellens
Apr 8, 2014·Breast Cancer Research and Treatment·Daniel L HertzHoward L McLeod
Feb 28, 2015·Nature Communications·Duygu SagCatherine C Hedrick
May 3, 2015·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Chris R CardwellLiam J Murray
Jul 2, 2015·PloS One·Andrew W BergenUNKNOWN Transdisciplinary Research in Cancer of the Lung Research Team
Aug 13, 2015·Pharmacogenomics·Annemieke J M NieuweboerRon H N van Schaik
Sep 9, 2015·The Pharmacogenomics Journal·A J M NieuweboerR H J Mathijssen
Nov 21, 2015·Cancer Treatment Reviews·C N FrederiksE Boven
Dec 15, 2015·Clinical Pharmacology and Therapeutics·C D DrenbergS D Baker
Jan 13, 2016·International Journal of Cancer. Journal International Du Cancer·Yanru WangQingyi Wei
Jan 17, 2016·Translational Research : the Journal of Laboratory and Clinical Medicine·Enrica RumiatoDaniela Saggioro
Jan 23, 2016·The Journal of Endocrinology·Kerryn M TaylorPaula Sommer
Apr 28, 2016·Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco·Yong Suk LeeEun-Cheol Park
Aug 9, 2016·Molecular and Cellular Endocrinology·Chrysovalantou MihailidouParaskevi Moutsatsou
Sep 11, 2016·Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco·Elizabeth K Do, Hermine H Maes

❮ Previous
Next ❯

Citations

Oct 30, 2020·Cancer Management and Research·Shunda WangYupei Zhao

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
genotyping
Assay

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.