A team of researchers at Case Western Reserve University School of Medicine have developed a novel method to disrupt this growth signaling pathway, with findings that suggest a new treatment for breast, colon, melanoma and other cancers.
The research team has pinpointed the cancer abnormality to a mutation in a gene called PIK3CA that results in a mutant protein, which may be an early cancer switch. By disrupting the mutated signaling pathway, the Case Western Reserve team, led by John Wang, PhD, inhibited the growth of cancer cells, opening the possibility to new cancer therapies.
Their findings, "Gain of interaction with IRS1 by p110á helical domain mutants is crucial for their oncogenic functions," was published on May 2 in the journal Cancer Cell.
Cancer arises from a single cell, which has mutated in a small number of genes because of random errors in the DNA replication process. These mutations play key roles in carcinogenesis.
"This discovery has a broad impact on the treatment of human cancer patients because so many cancers are affected by this particular mutation in the p110á protein, which is encoded by the PIK3CA gene," said Wang, an associate professor in the Department of Genetics and Case Comprehensive Cancer Center. "This is a significant advance because we can now disrupt this misdirected signaling pathway in cancer cells."
"If you turn on a light, you have to turn on a switch. But in the case of the mutation of this protein, p110á turns on by itself," Wang said. "The mutation rewires the circuit and is uncontrolled. This implies that if you break these wires, you can control the growth of cancer. Our current discovery may lead to finding less toxic drugs that can be used for personalized treatment for cancer patients in the future."
"This research will impact the field by focusing us on new targets for treating and preventing metastasis in patients in a many different types of human cancers," said Stanton Gerson, MD, Asa and Patricia Shiverick-Jane Shiverick (Tripp) Professor of Hematological Oncology, and director of Case Comprehensive Cancer Center and of Seidman Cancer Center at University Hospitals Case Medical Center.
Wang's multidisciplinary team of Case Western Reserve researchers includes: Yujun Hao, Chao Wang, Bo Cao, Brett M. Hirsch, Jing Song, Sanford D. Markowitz, Rob M. Ewing, David Sedwick, Lili Liu and Weiping Zheng.
About Case Western Reserve University School of Medicine
Founded in 1843, Case Western Reserve University School of Medicine is the largest medical research institution in Ohio and is among the nation's top medical schools for research funding from the National Institutes of Health. The School of Medicine is recognized throughout the international medical community for outstanding achievements in teaching. The School's innovative and pioneering Western Reserve2 curriculum interweaves four themes--research and scholarship, clinical mastery, leadership, and civic professionalism--to prepare students for the practice of evidence-based medicine in the rapidly changing health care environment of the 21st century. Nine Nobel Laureates have been affiliated with the School of Medicine.
Annually, the School of Medicine trains more than 800 MD and MD/PhD students and ranks in the top 25 among U.S. research-oriented medical schools as designated by U.S. News & World Report's "Guide to Graduate Education."
The School of Medicine's primary affiliate is University Hospitals Case Medical Center and is additionally affiliated with MetroHealth Medical Center, the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, and the Cleveland Clinic, with which it established the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in 2002. http://casemed.case.edu
About Case Comprehensive Cancer Center
Case Comprehensive Cancer Center is an NCI-designated Comprehensive Cancer Center located at Case Western Reserve University. The center, now in its 25nd year of funding, integrates the cancer research activities of the largest biomedical research and health care institutions in Ohio – Case Western Reserve, University Hospitals (UH) Case Medical Center and the Cleveland Clinic. NCI-designated cancer centers are characterized by scientific excellence and the capability to integrate a diversity of research approaches to focus on the problem of cancer. It is led by Stanton Gerson, MD, Asa and Patricia Shiverick- Jane Shiverick (Tripp) Professor of Hematological Oncology, director of the National Center for Regenerative Medicine, Case Western Reserve, and director of the Seidman Cancer Center at UH Case Medical Center
Christine A. Somosi | EurekAlert!
Antibiotic effectiveness imperiled as use in livestock expected to increase
27.03.2015 | Princeton University
A human respiratory tissue model to assess the toxicity of inhaled chemicals and pollutants
26.03.2015 | R&D at British American Tobacco
In an experiment at the Department of Energy's SLAC National Accelerator Laboratory, scientists precisely measured the temperature and structure of aluminum as...
The IPH presents a solution at HANNOVER MESSE 2015 to make ship traffic more reliable while decreasing the maintenance costs at the same time. In cooperation with project partners, the research institute from Hannover, Germany, has developed a sensor system which continuously monitors the condition of the marine gearbox, thus preventing breakdowns. Special feature: the monitoring system works wirelessly and energy-autonomously. The required electrical power is generated where it is needed – directly at the sensor.
As well as cars need to be certified regularly (in Germany by the TÜV – Technical Inspection Association), ships need to be inspected – if the powertrain stops...
When an earthquake hits, the faster first responders can get to an impacted area, the more likely infrastructure--and lives--can be saved.
The Atlantic overturning is one of Earth’s most important heat transport systems, pumping warm water northwards and cold water southwards. Also known as the Gulf Stream system, it is responsible for the mild climate in northwestern Europe.
Scientists now found evidence for a slowdown of the overturning – multiple lines of observation suggest that in recent decades, the current system has been...
Because they are regularly subjected to heavy vehicle traffic, emissions, moisture and salt, above- and underground parking garages, as well as bridges, frequently experience large areas of corrosion. Most inspection systems to date have only been capable of inspecting smaller surface areas.
From April 13 to April 17 at the Hannover Messe (hall 2, exhibit booth C16), engineers from the Fraunhofer Institute for Nondestructive Testing IZFP will be...
25.03.2015 | Event News
19.03.2015 | Event News
17.03.2015 | Event News
27.03.2015 | Agricultural and Forestry Science
27.03.2015 | Materials Sciences
27.03.2015 | Ecology, The Environment and Conservation