About My Health Careers Internship MedBlogs Contact us
Medindia LOGIN REGISTER
Advertisement

Vincristine Combined With a Novel Agent Knocks Out Ewing’s Sarcoma

by Anjali Aryamvally on October 7, 2017 at 4:16 PM
Font : A-A+

Vincristine Combined With a Novel Agent Knocks Out Ewing’s Sarcoma

Novel compound, YK-4-279, developed by team at Georgetown Lombardi Comprehensive Cancer Center, when combined with Vincristine halts the ability of Ewing sarcoma to grow and progress.

The finding, in cell lines and animal models, warrants clinical investigation to see if the combination would be an effective treatment as well as a less toxic alternative to current therapy for the rare bone cancer, the researchers say.

Advertisement


The study, published October 3 in the journal Science Signaling (Inhibition of the oncogenic fusion protein EWS-FLI1 causes G2-M cell cycle arrest and enhanced vincristine sensitivity in Ewing's sarcoma), tests a combination of YK-4-279, the compound developed at Georgetown, with vincristine in laboratory and mice studies. Vincristine is one of the chemotherapy drugs now used to treat Ewing sarcoma.

"Each of the two drugs impacts the cancer cell's ability to survive, but they do it in a way that magnifies their effectiveness compared to if they were used alone. It's like a left hook followed by an uppercut," says the study's senior investigator, Jeffrey Toretsky, MD, a pediatric oncologist and researcher at Georgetown Lombardi.
Advertisement

Ewing's Sarcoma

In the United States, about 500 children and young adults are diagnosed with Ewing sarcoma annually. Between 60 to 70 percent of patients survive more than five years, but with many late effects from treatment. Patients with Ewing sarcoma are currently treated with a combination of five different chemotherapy drugs, which often damages nerves and few treatments lead to a cure when the cancer progresses, Toretsky says.

Ewing sarcoma is caused by the exchange of DNA between two chromosomes. The resulting EWSR1-FLI1 gene produces a fusion protein, EWS-FLI1, responsible for cancer's growth. In 2006, Toretsky and his team discovered that the fusion protein binds to another protein, RNA helicase A (RHA), which is important for cancer progression.

YK-4-279 directly inhibits EWS-FLI1. Toretsky's work on YK-4-279 led to the eventual development of TK216, a first-in-class small molecule that is now being studied by Oncternal Therapeutics in a clinical trial in patients with relapsed or refractory Ewing sarcoma.

Overview of the study

In this study, Toretsky led a team of researchers that tested 69 different anti-cancer drugs to find an agent that would work synergistically with YK-4-279. They discovered that together, the drugs produce a "microtubule catastrophe" in Ewing sarcoma cancer cells.

Microtubules are tube-like structures that help cells keep their shape and act like highways that transport cellular proteins. They also pull apart chromosomes when they divide, and it is this action that is particularly affected by the drug combo, Toretsky says.

"Cancer needs to grow, and to do that, the cells need to divide and multiply. This is the step both drugs target, but in different ways," he says.

According to Toretsky, Oncternal is planning to test the combination of TK216 and vincristine in patients.



Source: Eurekalert
Advertisement

Advertisement
News A-Z
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Advertisement
News Category
What's New on Medindia
International Day of Persons with Disabilities 2021 - Fighting for Rights in the Post-COVID Era
Effect of Blood Group Type on COVID-19 Risk and Severity
Woman with Rare Spinal Cord Defect from Birth Sues Doctor
View all

Medindia Newsletters Subscribe to our Free Newsletters!
Terms & Conditions and Privacy Policy.

More News on:
Amyotrophic Lateral Sclerosis (ALS) Rhabdomyosarcoma Acute Coronary Syndrome 

Recommended Reading
Common Genetic Link Identified In Prostate Cancer And Ewing’s Sarcoma
Researchers find a common genetic link between molecular mechanisms in prostate cancer and Ewing's ....
Vincristine Induced Peripheral Neuropathy Linked With Gene Variant in Children With Acute Lymphoblastic Leukemia
Children with acute lymphoblastic leukemia who had a certain gene variant experienced a higher ......
Shedding Light on the Mutational Landscape of Acute Lymphoblastic Leukemia
Genomic alterations in pediatric relapsed acute lymphoblastic leukemia have been identified by ......
Soft Tissue Sarcoma
Soft tissue sarcoma is a rare cancer of connective tissue that can affect soft tissues such as fat, ...
Acute Coronary Syndrome
Acute coronary syndrome (ACS) is a sudden, acute life-threatening condition caused by a dramatic red...
Amyotrophic Lateral Sclerosis (ALS)
Find out more about the degenerative disease- Amyotrophic lateral sclerosis....
Rhabdomyosarcoma
Rhabdomyosarcoma is a rare type of cancer affecting the striated muscles. It mostly occurs in ......

Disclaimer - All information and content on this site are for information and educational purposes only. The information should not be used for either diagnosis or treatment or both for any health related problem or disease. Always seek the advice of a qualified physician for medical diagnosis and treatment. Full Disclaimer

© All Rights Reserved 1997 - 2021

This site uses cookies to deliver our services. By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use