Archives     Advertise     Editorial Calendar     Subscribe     Contact Us    



Vanderbilt Researchers Identify Protein's Possible Role in Chemotherapy Resistance


 
David Cortez, Ph.D.

Researchers at Vanderbilt University Medical Center (VUMC) have discovered a protein that may lead to a new way to prevent resistance and improve outcomes for patients whose cancers have mutations in the tumor suppressor gene BRCA2.

The protein, RADX, is a DNA-binding protein. It regulates the activity of an enzyme called RAD51, which helps repair tumor-promoting DNA breaks and ensure an accurate copy of the DNA is made during cell division. RAD51, in turn, is gathered up and transported to the sites of DNA damage and DNA replication by the BRCA2 protein.

Mutations in the BRCA2 gene disrupt the DNA repair and replication functions of the BRCA2/RAD51 pathway, increasing the risk of cancers of the breast, ovaries, prostate and pancreas as well as melanoma.

Since BRCA2 mutations also reduce the ability of tumor cells to repair broken DNA, these cells are sensitive to DNA-damaging anti-cancer drugs like cisplatin and newly approved DNA repair inhibitors like Olaparib. If the cells acquire secondary mutations that restore normal BRCA2 function, however, they can become resistant to the drugs.

This is the case with ovarian cancer. Within six months one quarter of ovarian tumors will become resistant to cisplatin. Only a third of patients survive beyond five years, making ovarian cancer the fifth-leading cause of cancer death among women in the United States.

RADX, the protein discovered by the Vanderbilt scientists, may be a key to understanding and overcoming this resistance.

In a paper published in the journal Molecular Cell, David Cortez, Ph.D., and colleagues describe how RADX regulates the activity of RAD51 in a way that promotes genome stability and modulates drug sensitivity.

Much remains to be learned. But if, as suspected, RADX determines how tumors respond to therapy, it could be a target for efforts to overcome resistance, the researchers concluded.

The paper's first authors were Huzefa Dungrawala, Ph.D., a postdoctoral fellow in Cortez's lab, and graduate student Kamakoti Bhat. Cortez is Ingram Professor of Cancer Research and professor of Biochemistry and co-leader of the Genome Maintenance Program in the Vanderbilt-Ingram Cancer Center.

The research was supported in part by National Institutes of Health grants GM116616, CA092584, CA212435 and GM118089.

 
Share:

Related Articles:


Recent Articles

Increasing Number Of Tennesseans Dying From Drug Overdoses

Tennessee Department of Health data show 1,631 Tennesseans died from drug overdoses in 2016, the highest annual number of such deaths recorded in state history. This is an increase from the 1,451 overdose deaths recorded among Tennessee residents in 2015.

Read More

AMA Urges Congress to Take Swift Action to Retain DACA Program Protections

The American Medical Association sent a letter to Congress on Sept. 5 outlining why DACA is an American healthcare issue and urging legislators to take prompt action to ensure individuals with Deferred Action for Childhood Arrivals status are able to remain in the United States.

Read More

New Antiviral Drug Inhibits Epidemic SARS, MERS & More

A multi-institutional team of researchers has found a new antiviral drug candidate that could treat or prevent a number of potential pandemic outbreaks.

Read More

Disaster Preparedness: Are We Ready?

In a world of ever-evolving threats, the officials responsible for a community's health and safety must constantly update, evaluate, prepare and communicate their preparedness plan.

Read More

Addressing Opioid Addiction in America

Even as the AMA works with physicians and other providers to address opioid addiction, the national epidemic continues to evolve.

Read More

Moving Forward on Health Reform

THA's Craig Becker shares the hospital perspective on healthcare reform and what's needed to maintain access to care across Tennessee.

Read More

MGMA Releases 2017 Regulatory Burden Survey: MIPS Tops the List

The results of the Medical Group Management Association (MGMA) 2017 Regulatory Burden Survey reveal there is no shortage of opportunity to reduce regulatory burdens on physician practices.

Read More

In Case of Emergency

On Sept. 8, 2016 the final rule Emergency Preparedness Requirements for Medicare and Medicaid Participating Providers and Suppliers was published in the Federal Register. By Nov. 16, 2017, providers and suppliers must be in compliance.

Read More

Innovative Meharry Program Helps Mothers with Opioid Addiction

The Rainbow Program at Meharry offers pregnant and postpartum women with substance abuse disorders new hope.

Read More

The Osher Center: Healing Mind, Body & Spirit

Multi-faceted approach to pain management blends old and new therapies at The Osher Center for Integrative Medicine at Vanderbilt

Read More

Email Print
 
 

 

 


Tags:
None
Powered by Bondware
News Publishing Software

The browser you are using is outdated!

You may not be getting all you can out of your browsing experience
and may be open to security risks!

Consider upgrading to the latest version of your browser or choose on below: