Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Compound from marine bacteria shows potential as multiple myeloma therapy


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:

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 >>>