Navigation Links
New drug agent knocks out multiple enzymes in cancer pathway
Date:3/25/2009

A team of 24 researchers from the U.S., Europe, Taiwan and Japan and led by University of Illinois scientists has engineered a new anti-cancer agent that is about 200 times more active in killing tumor cells than similar drugs used in recent clinical trials.

The study appears this week in the Journal of the American Chemical Society.

The new agent belongs to a class of drugs called bisphosphonates. These compounds were originally developed to treat osteoporosis and other bone diseases, but were recently found to also have potent anti-cancer and immune boosting properties.

Drug developers have tried for years to design drugs to inhibit cell survival pathways in tumor cells, focusing on a protein called Ras since nearly a third of all human cancers involve a mutation in the Ras gene that causes cell signaling to go awry. These efforts have met with limited success.

Bisphosphonates act on other enzymes, called FPPS and GGPPS, which are upstream of Ras in the cell survival pathway. Inhibiting these enzymes appears to be a more effective strategy for killing cancer cells.

When used in combination with hormone therapy in a recent clinical trial, the bisphosphonate drug zoledronate significantly reduced the recurrence of breast cancer in premenopausal women with estrogen-receptor-positive breast cancer. Similar results were reported previously for hormone-refractory prostate cancer.

But zoledronate quickly binds to bone, reducing its efficacy in other tissues.

"We're trying to develop bisphosphonates that will be very active but won't bind to the bone, because if they bind to the bone they're not going to go to breast, lung or other tissues," said University of Illinois chemistry professor Eric Oldfield, who led the new study.

Oldfield's team also wanted to design a compound that would inhibit multiple enzymes in the tumor cell survival pathway, rather than just one, an approach analogous to the use of multi-kinase inhibitors in cancer therapy.

Andrew Wang, of Academia Sinica, Taipei, and Illinois chemist Rong Cao began by producing crystallographic structures of the target enzymes and drug candidates, allowing the researchers to identify those features that would enhance the drugs' ability to bind to the enzymes. Using this and other chemical data, Illinois chemistry department research scientist Yonghui Zhang engineered new bisphosphonate compounds that bound tightly to multiple enzyme targets, but not to bone.

One of the new compounds, called BPH-715, proved to be especially potent in cell culture and effectively inhibited tumor cell growth and invasiveness.

Tadahiko Kubo, of Hiroshima University, then found that BPH-715 also killed tumor cells in mice. And Socrates Papapoulos, of Leiden University, the Netherlands, showed that the compound had a very low chemical affinity for bone.

In humans, compounds like BPH-715 and zoledronate have an added benefit in fighting cancer: They spur the proliferation of immune cells called gamma delta T-cells, which aid in killing tumor cells.

"The new drugs are about 200 times more effective than the drugs used in recent clinical trials at killing tumor cells and in activating gamma delta T-cells to kill tumor cells," Oldfield said. "They also prevent tumor progression in mice much better than do existing bisphosphonate molecules."


'/>"/>

Contact: Diana Yates
diya@illinois.edu
217-333-5802
University of Illinois at Urbana-Champaign
Source:Eurekalert  

Related biology news :

1. Structure of enzyme against chemical warfare agents determined
2. Chemopreventive agents in black raspberries identified
3. MIT nanotubes sniff out cancer agents in living cells
4. Exposure to Agent Orange linked to prostate cancer in Vietnam veterans
5. Certain anticancer agents could be harmful to patients with heart disease
6. UF researchers develop improved gene therapy agent
7. New insights into the diversity of Creutzfeldt-Jakob disease agents
8. Drug aimed at 2 bioterror agents blocks live viral infection, Weill Cornell team reports
9. Contrast agent trials in swine
10. Agent that triggers immune response in plants is uncovered
11. Primate behavior explained by computer agents
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
New drug agent knocks out multiple enzymes in cancer pathway
(Date:4/28/2016)... , April 28, 2016 First quarter 2016: ... up 966% compared with the first quarter of 2015 ... SEK 589.1 M (loss: 18.8) and the operating margin was 40% ... 0.32) Cash flow from operations was SEK 249.9 M ... revenue guidance is unchanged, SEK 7,000-8,500 M. The operating ...
(Date:4/15/2016)... CHICAGO , April 15, 2016  A ... companies make more accurate underwriting decisions in a ... offering timely, competitively priced and high-value life insurance ... health screenings. With Force Diagnostics, rapid ... and lifestyle data readings (blood pressure, weight, pulse, ...
(Date:3/31/2016)...   LegacyXChange, Inc. ... LegacyXChange is excited to release its first ... be launched online site for trading 100% guaranteed authentic ... also provide potential shareholders a sense of the value ... industry that is notorious for fraud. The video is ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... 2016 Andrew D ... http://doi.org/10.17925/OHR.2016.12.01.22 Published recently in ... from touchONCOLOGY, Andrew D Zelenetz , discusses ... care is placing an increasing burden on healthcare ... therapies. With the patents on many biologics expiring, ...
(Date:6/23/2016)... (PRWEB) , ... June 23, 2016 , ... ... a new line of intelligent tools designed, tuned and optimized exclusively for Okuma ... 12–17 in Chicago. The result of a collaboration among several companies with expertise ...
(Date:6/22/2016)... June 22, 2016 Research and Markets has ... report to their offering. ... 2014 from $29.3 billion in 2013. The market is expected to ... from 2015 to 2020, increasing from $50.6 billion in 2015 to ... forecasts during the forecast period (2015 to 2020) are discussed. As ...
(Date:6/22/2016)... 2016   ViaCyte, Inc. , a privately-held regenerative ... replacement therapy for the treatment of diabetes in clinical-stage ... Meeting.  ISSCR 2016, the Global Stem Cell Event, is ... in San Francisco.    ... follows:Event: , Focus Session: Tools for Basic and Applied ...
Breaking Biology Technology: