Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Compound from marine bacteria shows potential as multiple myeloma therapy

15.11.2005


Kills blood cancer cells with low toxicity in preclinical studies



An anti-cancer compound derived from bacteria dwelling in ocean-bottom sediments appears in laboratory tests to be a potent killer of drug-resistant multiple myeloma cells, and potentially with less toxicity than current treatments, report Dana-Farber Cancer Institute researchers in the November issue of Cancer Cell.

The experimental compound, NPI-0052, has been found to block or inhibit cancer cells’ proteasomes from working effectively. The proteasome work as a cell’s "garbage disposal," chewing up and disposing of old, unwanted proteins. With their proteasome jammed, cells die from the backup of damaged proteins.


"Proteasome inhibition is a key therapeutic target and bortezomib (Velcade tm) was the first in a new class of compounds in multiple myeloma. NPI-0052 is a novel proteasome inhibitor with a chemical structure and action that is distinct from bortezomib, and has the promise of being even more effective for patients," says Kenneth Anderson, MD, director of the Jerome Lipper Multiple Myeloma Center at Dana-Farber, and senior author of the report.

The compound will be moved into Phase I clinical trials in early 2006, say officials of Nereus Pharmaceuticals in San Diego, the developer of NPI-0052. The compound will be tested as a single agent and subsequently in combination with other treatments.

Multiple myeloma is a currently incurable cancer of the bone marrow that causes a plunge in the production of vital red and white blood cells. Although relatively rare, it is the second most common type of blood cancer and accounts for 11,000 deaths annually in the United States. Bortezomib, approved by the Food and Drug Administration in 2003 for relapsed myeloma patients and subsequently for patients who have received at least one prior treatment, demonstrated in clinical trials that it extended the time to disease progression and also improved survival.

Though less toxic than conventional chemotherapy, bortezomib does have significant side effects in some myeloma patients, including altered blood counts and nerve pain. In some patients, the disease can be resistant or become resistant to bortezomib.

Because NPI-0052 and bortezomib attack the same intracellular target in different ways, the Dana-Farber researchers contend that combining these two agents might be more effective than using either therapy alone – and be better tolerated by patients as well.

In preclinical studies, NPI-0052 blocks a wider range of proteasome activities than bortezomib, say the researchers, and works at lower doses. NPI-0052 also appears to be less toxic to normal cells. Bortezomib is currently given by intravenous infusion. "NPI-0052 can be given orally, although the first clinical trials will be using the intravenous route," says Paul Richardson, M.D, who is also a co-author in this study and will be leading the Phase-I clinical trial in myeloma at Dana-Farber.

NPI-0052 was discovered by William Fenical, PhD, and his collaborators at The Scripps Institute of Oceanography during the fermentation of Salinispora, a new class of marine gram-positive bacteria identified in sediment samples from the ocean floor. The substance has shown strong anticancer properties in laboratory tests. Nereus Pharmaceuticals holds an exclusive license to the compound for drug development.

Experiments with NPI-0052 began at Dana-Farber in 2003, said Dharminder Chauhan, PhD, lead author of the paper along with Laurence Catley, PhD. When added to cells from patients whose disease was resistant to both standard drugs and bortezomib, the compound efficiently killed the cells. Analyses showed that NPI-0052 and bortezomib express different profiles for inhibiting the three major proteasome activities.

In mice implanted with human myeloma tumor cells, NPI-0052 was well tolerated, prolonged survival and significantly reduced the rate of cancer recurrences. Because NPI-0052 and bortezomib block the proteasome in different ways, the researchers tested them together on myeloma cells. They found that the cancer cells were killed more effectively by the combination than either compound alone – without additional toxicity to normal cells.

"This is a laboratory advance that shows clinical promise," says Dr. Chauhan. "We think this is going to be the ’2006 Model’ of proteasome inhibitors."

Michael Palladino, Jr., PhD, chief technical officer of Nereus Pharmaceuticals, said that the company plans to file an investigational new drug (IND) application by the end of the year, with trials at several centers – including Dana-Farber – starting in early 2006.

Teresa Herbert | EurekAlert!
Further information:
http://www.dana-farber.org

More articles from Life Sciences:

nachricht Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover

nachricht First transcription atlas of all wheat genes expands prospects for research and cultivation
17.08.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Smallest transistor worldwide switches current with a single atom in solid electrolyte

17.08.2018 | Physics and Astronomy

Robots as Tools and Partners in Rehabilitation

17.08.2018 | Information Technology

Climate Impact Research in Hannover: Small Plants against Large Waves

17.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>