Ruxolitinib synergistically enhances the anti-tumor activity of paclitaxel in human ovarian cancer.

Oncotarget
Ernest S HanJohn H Yim

Abstract

Treatment for ovarian cancer remains challenging despite a high initial response rate to first line platinum-taxane treatment. Most patients eventually experience recurrence and require further treatment. Persistent activation of STAT3 is associated with cancer growth and progression and is also involved in cell resistance to platinum and taxane treatment. Targeting JAK/STAT3, therefore, could be a potential novel therapeutic approach for treating advanced and chemoresistant ovarian cancer. We investigated the therapeutic potential of ruxolitinib, a JAK1/JAK2 inhibitor that has been FDA-approved for the treatment of myelofibrosis, to treat ovarian cancer either alone or in combination with conventional chemotherapy agents. We show that ruxolitinib inhibits STAT3 activation and ovarian tumor growth both in ovarian cancer cells and in an ovarian cancer mouse model. In addition, ruxolitinib significantly increases the anti-tumor activity of chemotherapy agents, including paclitaxel, cisplatin, carboplatin, doxorubicin and topotecan in ovarian cancer cells. Evaluation of the combination index (CI) shows that ruxolitinib synergistically interacts with paclitaxel in all three human ovarian cancer cells. Finally, our results demonstra...Continue Reading

References

Sep 12, 1997·Science·J E Darnell
Aug 24, 1999·Cell·J F BrombergJ E Darnell
Feb 18, 2004·Nature Reviews. Cancer·Hua Yu, Richard Jove
Dec 14, 2004·The New England Journal of Medicine·Stephen A Cannistra
Jun 7, 2005·Nature Medicine·James E Darnell
Sep 5, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Zhenfeng DuanMichael V Seiden
Oct 24, 2009·Nature Reviews. Cancer·Hua YuRichard Jove
Nov 12, 2009·Cancer Research·Christine E BrownMichael C Jensen
Apr 7, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jordan S FridmanKris Vaddi
Feb 15, 2011·Cancer Biology & Therapy·Gil MorAyesha Alvero
Feb 24, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michael S AnglesioDavid D Bowtell
May 1, 2010·Therapeutic Advances in Medical Oncology·Mihaela CristeaRobert J Morgan
Sep 24, 2011·Nature Reviews. Cancer·Sebastian VaughanFrances R Balkwill
Dec 14, 2011·Gynecologic Oncology·Robert A Burger
Dec 30, 2011·The New England Journal of Medicine·Robert A BurgerUNKNOWN Gynecologic Oncology Group
Feb 23, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Pasquale Sansone, Jacqueline Bromberg
Mar 2, 2012·The New England Journal of Medicine·Srdan VerstovsekHagop M Kantarjian
Feb 15, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alfonso Quintás-Cardama, Srdan Verstovsek
Sep 13, 2014·Apoptosis : an International Journal on Programmed Cell Death·Yuan HuYibang Chen
Oct 25, 2014·Nature Reviews. Cancer·Hua YuRichard Jove
Sep 10, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Herbert I HurwitzRichard S Levy
Nov 19, 2015·Trends in Pharmacological Sciences·Chengguang ZhaoGuang Liang
Jan 6, 2016·ACS Chemical Biology·Steffanie L FurtekPhilip Reigan
Jan 27, 2016·Proceedings of the National Academy of Sciences of the United States of America·Wei JuThomas A Waldmann
Feb 10, 2016·Cancer Cell·Ilaria IacobucciCharles G Mullighan
Jul 6, 2016·Frontiers in Oncology·Mehrad TavallaiPaul Dent

❮ Previous
Next ❯

Citations

Feb 20, 2020·Journal of Cellular Physiology·Arezoo HosseiniBehzad Baradaran
Jul 15, 2020·Current Medicinal Chemistry·Manuel TorralbaGabriele Grassi

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
acid
fluorescence-activated cell sorting
protein assay

Clinical Trials Mentioned

NCT01773187
NCT00935987

Software Mentioned

Calcusyn

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.