Corporate Banner
Satellite Banner
Biomolecular Screening
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Scientists Find a New Way to Boost Common Cancer Drugs

Published: Wednesday, January 16, 2013
Last Updated: Wednesday, January 16, 2013
Bookmark and Share
Blocking a particular pathway in the cell makes it easier for drugs to annihilate tumors.

Shutting down a specific pathway in cancer cells appears to improve the ability of common drugs to wipe those cells out, according to new research from scientists at Fox Chase Cancer Center, published in the January issue of Cancer Discovery.

"Ideally, this research will eventually enable scientists to find drugs that disrupt this pathway and boost the impact of current therapies," says Igor Astsaturov, MD, PhD, Attending Physician in the Department of Medical Oncology at Fox Chase. "That's the long-term plan."

The new approach appears to enhance the tumor-killing ability of a commonly prescribed class of drugs that includes cetuximab (Erbitux), used to treat colorectal and head and neck cancers. These drugs work by blocking the activity of the epidermal growth factor receptor (EGFR), which sits on the cell surface and senses cues from the environment, telling cancer cells to grow and divide, says Astsaturov. "The whole mantra of modern day oncology is to suppress these inputs."

Although EGFR inhibitors succeed in killing cancer cells, some malignant cells still find ways to evade the drug, and become resistant to treatment. Consequently, many researchers are actively looking for ways to kill these surviving cancer cells, annihilating tumors completely.

In 2010, Astsaturov and his colleagues identified a pathway in the cell that, when blocked, completely suppressed EGFR activity. Interestingly, the pathway consists of a series of enzymes that, when working in concert, synthesize new molecules of cholesterol, an essential component of the cell wall. This pathway is particularly important to cancer cells, which are constantly dividing and therefore need to produce more cholesterol for the new cells.

Working with cancer cells in the lab, the researchers inactivated a key gene in the cholesterol synthesis pathway, and found the cells became more vulnerable to treatment with cetuximab. The same was true in mice that lacked this particular pathway, says Astsaturov. "Most tumors are only moderately sensitive to inhibitors of EGFR, but when these tumors lack an essential gene in the cholesterol pathway, they become exquisitely sensitive to the anti-EGFR drugs," he says. "The cancers literally melt away in mice."

The researchers then removed one of the cholesterol genes from the mouse genome, and saw that mice developed patchy, scaly skin. When they biopsied this affected skin, they saw no activity of the EGFR protein, reaffirming that shutting down cholesterol synthesis interrupts EGFR. They also observed the same pattern in normal cell lines.

When the cholesterol biosynthesis pathway is blocked, explains Astsaturov, the normal chain of events that creates a cholesterol molecule is interrupted, and cells accumulate intermediate products of cholesterol that block the normal movement of substances around the cell. This cellular traffic jam makes it difficult for the cell to transport important components, such as EGFR, which has to move between the inside of the cell and its surface to function properly. "If you disrupt this traffic, the cancer cells don't survive."

Eventually, says Astsaturov, researchers can design drugs or look for existing ones that block this cholesterol synthesis pathway. For now, his lab is trying to uncover more details of how the pathway works, the role of each protein that is involved—and whether if, by blocking a protein, they can wipe out tumors in humans that evade current therapies. "These proteins represent targets for additional drugs, which could be combined with EGFR inhibitors," he says.

Astsaturov's co-authors include Erica A. Golemis, Anna Sukhanova, Andrey Gorin, Ilya G. Serebriiskii, Linara Gabitova, Hui Zheng, Diana Restifo, Tetyana Bagnyukova, Hanqing Liu, Anna Nikonova, Gregory P. Adams, Yan Zhou, Ranee Mehra, Barbara Burtness, Kathy Q. Cai, Andres Klein-Szanto, and Brian L. Egleston, Fox Chase; David Cunningham and Gail E. Herman, The Research Institute at Nationwide Children’s Hospital and the Department of Pediatrics; Lisa E. Kratz, Richard I. Kelley, The Ohio State University; and Louis M. Weiner, Lombardi Comprehensive Cancer Center.


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,400+ scientific posters on ePosters
  • More than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.


Scientific News
Liquid Biopsies: Utilization of Circulating Biomarkers for Minimally Invasive Diagnostics Development
Market Trends in Biofluid-based Liquid Biopsies: Deploying Circulating Biomarkers in the Clinic. Enal Razvi, Ph.D., Managing Director, Select Biosciences, Inc.
Lab-on-a-Chip Offers Promise for TB and Asthma Patients
A device to mix liquids using ultrasonics is the first and most difficult component in a miniaturized system for low-cost analysis of sputum from patients with pulmonary diseases such as tuberculosis and asthma.
Protein Related to Long Term Traumatic Brain Injury Complications Discovered
NIH-study shows protein found at higher levels in military members who have suffered multiple TBIs.
Urine Proteins Point to Early-Stage Pancreatic Cancer
A combination of three proteins found at high levels in urine can accurately detect early-stage pancreatic cancer, researchers at the BCI have shown.
Researcher Discovers Trigger of Deadly Melanoma
New research sheds light on the precise trigger that causes melanoma cancer cells to transform from non-invasive cells to invasive killer agents, pinpointing the precise place in the process where "traveling" cancer turns lethal.
Crystal Clear Images Uncover Secrets of Hormone Receptors
NIH researchers gain better understanding of how neuropeptide hormones trigger chemical reactions in cells.
New Tool Uses 'Drug Spillover' to Match Cancer Patients with Treatments
Researchers have developed a new tool that improves the ability to match drugs to disease: the Kinase Addiction Ranker (KAR) predicts what genetics are truly driving the cancer in any population of cells and chooses the best "kinase inhibitor" to silence these dangerous genetic causes of disease.
HIV Susceptibility Linked to Little-Understood Immune Cell Class
High levels of diversity among immune cells called natural killer cells may strongly predispose people to infection by HIV, and may be driven by prior viral exposures, according to a new study.
Sweet Revenge Against Superbugs
A special type of synthetic sugar could be the latest weapon in the fight against superbugs.
Access Denied: Leukemia Thwarted by Cutting Off Link to Environmental Support
A new study reveals a protein’s critical – and previously unknown -- role in the development and progression of acute myeloid leukemia (AML), a fast-growing and extremely difficult-to-treat blood cancer.
SELECTBIO

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!