Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


St. Jude announces breakthrough in eye cancer treatment

Researchers use new, localized treatment to shrink retinoblastoma tumors, avoid chemo; treatment could be effective against some breast, lung, prostate and colon cancers

Scientists at St. Jude Children's Research Hospital have demonstrated in a mouse model a new, locally applied treatment for the eye cancer retinoblastoma that not only greatly reduces the size of the tumor, but does so without causing the side effects common with standard chemotherapy. The treatment also appears to be suitable for certain forms of breast, lung, prostate and colon cancer, and is simple enough for widespread use even in countries with limited resources.

A report on this work appears in the Nov. 2 issue of the journal Nature.

Retinoblastoma occurs in about 5,000 young children worldwide each year, arising from the immature retina, which is the part of the eye responsible for detecting light and color. The cancer is fatal if left untreated.

The new treatment holds promise for a simpler, more effective and less-toxic treatment for retinoblastoma that would eliminate the need for the current, complex therapy, according to senior author Michael Dyer, Ph.D., a Pew Scholar and associate member of the St. Jude Department of Developmental Neurobiology. The treatment is based on a discovery by Dyer's laboratory that overturned a widely held belief about the process of apoptosis (cell suicide) in retinoblastoma. Apoptosis is the way the body rids itself of abnormal cells that might become cancerous or cause other problems.

Until now, retinoblastoma experts thought that a mechanism called the p53 pathway triggered apoptosis in other types of cancer cells, but not in retinoblastoma. However, the St. Jude team proved not only that the p53 pathway was activated in early-stage retinoblastoma, but that excessive levels of a molecule called MDMX blocked it from triggering apoptosis in more advanced tumors. Based on this discovery, the St. Jude team used a molecule called nutlin-3 to block MDMX in retinoblastoma cells in test tube studies as well as in mouse models. The molecule was originally developed by

Roche Pharmaceuticals (Nutley, N.J.) for a similar use against a related target called MDM2 in adult cancer cells. The success in knocking out MDMX with nutlin-3 represents the first example of local delivery of a targeted chemotherapy drug for any childhood cancer, Dyer said.

Targeted therapy uses a customized drug to disable a specific molecule inside a growing cancer cell; local delivery is the placement of a drug at the site of disease, rather than systemic treatment. In systemic treatment, such as chemotherapy, a drug is infused into the body through a vein and then circulates, often causing toxic side effects that are especially challenging in children.

After demonstrating that nutlin-3 is effective when applied directly to the eye, the St. Jude team modified the treatment by combining this molecule with topotecan, a drug also being investigated in the treatment of retinoblastoma. Local delivery of this two-drug targeted treatment was even more effective, reducing tumor size significantly more than the most effective known combination of standard chemotherapy drugs.

"The findings suggest that this treatment not only could offer children with retinoblastoma more effective and less-toxic treatment," Dyer said. "It could also increase the chance that their vision can be preserved by eliminating the tumor and preventing its spread from the eye to the rest of the body."

The discovery that blocking MDMX releases the apoptosis response in retinoblastoma has important implications for certain forms of adult cancers as well. "Some forms of breast, lung, prostate and colon cancer are caused by abnormally large quantities of MDMX in the cells," Dyer explained. "So knocking out MDMX in those cancers might also dramatically reduce tumor size. And administering the drug directly to the site of the tumor could make the treatment especially effective while avoiding the toxicity caused by systemic exposure." This could mean the eventual elimination of all-body chemotherapy for certain cancers.

This work is likely to have its biggest impact on the care of children with retinoblastoma internationally, according to Dyer. Most children in the United States with retinoblastoma do not die from the disease because they benefit from early detection and advanced medical treatment. The complex treatment includes chemotherapy, radiation and laser therapy, as well as control of infections caused by treatment-related suppression of the immune system. However, most of the 5,000 children worldwide who are found to have retinoblastoma live primarily in countries with limited resources and have restricted access to medical treatment, according to Carlos Rodriguez-Galindo, M.D., an associate member of the St. Jude Oncology department.

"Today, those children do not have access to the advanced treatments available in other countries, such as the United States," Rodriguez-Galindo said, "but our new approach has the potential to make the treatment of retinoblastoma simpler and less toxic. Ideally, these treatments could be administered even in countries that cannot afford the highly complex infrastructure now required to manage children with retinoblastoma. This would mean saving many more lives and preserving more vision." Rodriguez-Galindo is a co-author of the paper.

Retinoblastoma can occur as a unilateral (one eye) or bilateral (both eyes) disease. In the case of unilateral disease, surgeons generally remove the eye that has the cancer in order to prevent the disease from spreading. However, children with bilateral retinoblastoma pose a significant challenge to physicians, who are reluctant to remove both eyes from young children, said Matthew Wilson, M.D., a surgeon in the St. Jude ophthalmology division and a co-author of the paper. In those cases, the physicians institute aggressive systemic chemotherapy to reduce the size of the tumor, followed by one of several possible therapies such as radiation or lasers to destroy the remaining cancer cells in the eye. "When successful, this therapy often saves vision," Wilson said. "Clinicians at major medical institutions generally save 70 percent of all eyes treated, even in the case of advanced disease."

Bonnie Kourvelas | EurekAlert!
Further information:

Further reports about: Cancer Dyer MDMX apoptosis chemotherapy retinoblastoma systemic

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>