Developing a genetic signature to predict drug response in ovarian cancer

Oncotarget
Stephen HyterAndrew K Godwin

Abstract

There is a lack of personalized treatment options for women with recurrent platinum-resistant ovarian cancer. Outside of bevacizumab and a group of poly ADP-ribose polymerase inhibitors, few options are available to women that relapse. We propose that efficacious drug combinations can be determined via molecular characterization of ovarian tumors along with pre-established pharmacogenomic profiles of repurposed compounds. To that end, we selectively performed multiple two-drug combination treatments in ovarian cancer cell lines that included reactive oxygen species inducers and HSP90 inhibitors. This allowed us to select cell lines that exhibit disparate phenotypes of proliferative inhibition to a specific drug combination of auranofin and AUY922. We profiled altered mechanistic responses from these agents in both reactive oxygen species and HSP90 pathways, as well as investigated PRKCI and lncRNA expression in ovarian cancer cell line models. Generation of dual multi-gene panels implicated in resistance or sensitivity to this drug combination was produced using RNA sequencing data and the validity of the resistant signature was examined using high-density RT-qPCR. Finally, data mining for the prevalence of these signatures in ...Continue Reading

Citations

Jun 1, 1976·Annals of the Rheumatic Diseases·A E FinkelsteinA Misher
Apr 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·Andrew K GodwinM E Anderson
Sep 13, 2001·Proceedings of the National Academy of Sciences of the United States of America·T SørlieA L Børresen-Dale
Mar 1, 2002·The New England Journal of Medicine·David G Savage, Karen H Antman
Aug 16, 2002·The New England Journal of Medicine·George D DemetriHeikki Joensuu
Mar 9, 2005·Cancer Research·Michelle B MintzDietrich A Stephan
Feb 27, 2007·Free Radical Biology & Medicine·Christine MarzanoMaria Pia Rigobello
Aug 14, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Richard W TothillDavid D L Bowtell
Jun 25, 2009·BMC Genomics·Uma T ShankavaramJohn N Weinstein
Feb 20, 2010·Nature Reviews. Drug Discovery·Steven M PaulAaron L Schacht
Apr 17, 2010·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Wouter B NagengastElisabeth G E de Vries
May 6, 2010·Molecular Cancer Therapeutics·Hongfang LiuWilliam C Reinhold
Feb 8, 2011·CA: a Cancer Journal for Clinicians·Ahmedin JemalDavid Forman
May 4, 2011·Environmental and Molecular Mutagenesis·Brinda MahadevanAnn M Richard
Jul 2, 2011·Nature·Cancer Genome Atlas Research Network
Aug 17, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Melissa A FathDouglas R Spitz
Dec 21, 2011·Nature Reviews. Gastroenterology & Hepatology·Nardin Samuel, Thomas J Hudson
Jan 5, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Len Neckers, Paul Workman
Jan 30, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hao TangYang Xie
May 10, 2013·Molecular Cancer Therapeutics·Ziyan Y PessettoAndrew K Godwin
Jun 13, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Cristiana SessaUdai Banerji
Jul 11, 2013·Nature Communications·Silvia DomckeNikolaus Schultz
Aug 1, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hanqing LiuDenise C Connolly
Sep 28, 2013·Nature Genetics·Cancer Genome Atlas Research NetworkJoshua M Stuart
Oct 3, 2013·Scientific Reports·Melissa S ClineJingchun Zhu
Nov 1, 2013·Molecular Cancer Research : MCR·Yin WangAlan P Fields

Related Concepts

Ovarian Diseases
Real-Time Polymerase Chain Reaction
Drug Response
Biochemical Pathway
Polymerase
Genes
Sequence Determinations, RNA
Ovarian Neoplasm
PRKCI gene
Inhibitors

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.

Sexual Dimorphism in Neurodegeneration

There exist sex differences in neurodevelopmental and neurodegenerative disorders. For instance, multiple sclerosis is more common in women, whereas Parkinson’s disease is more common in men. Here is the latest research on sexual dimorphism in neurodegeneration

HLA Genetic Variation

HLA genetic variation has been found to confer risk for a wide variety of diseases. Identifying these associations and understanding their molecular mechanisms is ongoing and holds promise for the development of therapeutics. Find the latest research on HLA genetic variation here.

Super-resolution Microscopy

Super-resolution microscopy is the term commonly given to fluorescence microscopy techniques with resolutions that are not limited by the diffraction of light. Here are the latest discoveries pertaining to super-resolution microscopy.

Genetic Screens in iPSC-derived Brain Cells

Genetic screening is a critical tool that can be employed to define and understand gene function and interaction. This feed focuses on genetic screens conducted using induced pluripotent stem cell (iPSC)-derived brain cells.

Brain Lower Grade Glioma

Low grade gliomas in the brain form from oligodendrocytes and astrocytes and are the slowest-growing glioma in adults. Discover the latest research on these brain tumors here.

CD4/CD8 Signaling

Cluster of differentiation 4 and 8 (CD8 and CD8) are glycoproteins founds on the surface of immune cells. Here is the latest research on their role in cell signaling pathways.

Alignment-free Sequence Analysis Tools

Alignment-free sequence analyses have been applied to problems ranging from whole-genome phylogeny to the classification of protein families, identification of horizontally transferred genes, and detection of recombined sequences. Here is the latest research.

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.

Related Papers

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Gottfried E Konecny
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Elizabeth H StoverElizabeth M Swisher
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Federica TomaoPierluigi Benedetti Panici
© 2020 Meta ULC. All rights reserved