Navigation Links
First-ever Compounds To Target Only Metastatic Cells Are Highly Effective Against Breast, Prostate, And Colon Cancers

Two compounds that zero in on cancer cells spreading throughout the body, while ignoring primary tumor cells, could someday give doctors a whole new weapon in the fight against tough-to-treat metastatic disease, according to Weill Medical College of Cornell University researchers.

The compounds, called synthetic migrastatin analogues, prevented 91 to 99 percent of metastatic breast cancer cells in mice, and are the first to target only metastatic cells.

"They're unbelievably effective, and in vitro study suggests they'll work just as well at inhibiting the migration of prostate and colon cancer cells," said senior researcher Dr. Xin-Yun Huang, Professor of Physiology and Biophysics at Weill Cornell Medical College in New York City.

The findings have just been published in Proceedings of the National Academy of Sciences.

For decades, doctors have fought cancer by using surgery, chemotherapy, or radiation to excise or shrink the primary tumor.

"However, in too many cases it's simply impossible to completely remove the tumor," Dr. Huang explained. "So recently the idea of targeting cell migration -- metastasis -- has become an alternative strategy that's gained a lot of interest among researchers."

If compounds could be found that slowed or halted cancer spread, doctors could gain valuable time in shrinking the primary tumor. "If we had the luxury of time, we could treat that primary tumor at lower doses, too, with fewer side effects for the patient," Dr. Huang said.

Until now, agents that specifically target metastatic cells have remained elusive. However, a new avenue of research opened up when Dr. Huang's team noticed that the Streptomyces bacterium -- the bug that gives us the antibiotic streptomycin -- also produces a natural compound called migrastatin, which appears to inhibit cell migration.

Natural migrastatin's effect is relatively weak, but Dr. Huang suspected the molecule might be manipulated in to something more potent. In collaboration with the laboratory of Dr. Samuel Danishefsky at the Memorial Sloan-Kettering Cancer Center, the team went to work creating what's called a "synthetic analogue."

"Starting with the basic migrastatin molecule, we cut a piece there, add a piece here," he explained, "and what we ended up with were two compounds -- core macroketone and core macrolactam -- that are about 1,000 times more powerful at inhibiting cancer cell migration."

In fact, in a mouse model, the analogues were between 91 to 99 percent effective in stopping the spread of breast cancer cells, the researchers report. Cell culture studies suggest they can reproduce that success in a wide range of other cancers, too.

"What's unique about these analogues is that they do all this without affecting primary tumor cells, or their blood supply," Dr. Huang said. "To our knowledge, that's a real first."

Exact mechanisms remain unclear.

"Obviously, these compounds are targeting some step in the cell-migration process," Dr. Huang said. The activity of a migration-linked protein called Rac appears to be much reduced in cancer cells affected by the analogues, and the researchers also noticed that malignant cells failed to grow tiny "antennas," called lamellipodia, another crucial step in the migration process.

"Therefore, the migrastatin analogues must be working on something upstream of those two important steps," Dr. Huang said.

Dr. HuangÕs next important step is moving these analogues into clinical trials.

"We're trying right now to get a company interested in this, especially because the mice used in our trial seemed to experience minimal toxicity -- a good sign that patients might tolerate these compounds, too," Dr. Huang said.

"It's all very exciting," he said. "Metastatic disease is such a tough problem, and these compounds could provide patients with a brand new kind of hope."

The research was funded by grants from the National Institutes of Health.

Co-researchers included Ms. Dandan Shan (first author), Mr. Lin Chen, and Dr. Xiaojing Ma, of Weill Cornell Medical College; and Dr. Jon T. Njardarson, Dr. Christoph Gaul, and Dr. Samuel Danishefsky, of Memorial Sloan-Kettering Cancer Center, New York.


'"/>

Source:Cornell University


Related biology news :

1. First-ever genomic test predicts which lung cancer patients need chemotherapy to live
2. Compounds in plastic packaging act as environmental estrogens altering breast genes
3. Novel Enzyme Shows Potential As An Anti-HIV Target
4. Potential Drug Target For Treating Cocaine Abuse Found
5. Affymetrix and ParAllele Launch Industrys Most Comprehensive Product Line for Targeted Genotyping
6. Targeting a key enzyme with gene therapy reversed course of Alzheimers disease in mouse models
7. New Therapeutic Target Identified In Inherited Brain Tumor Disorder
8. Targeted drug delivery achieved with nanoparticle-aptamer bioconjugates
9. Targeted virus compels cancer cells to eat themselves
10. Best of both worlds -- Targeting a single gene could inhibit bone decay and stimulate bone growth
11. Targeting tumors the natural way
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:9/15/2018)... , ... September 14, 2018 , ... The first ever ... of clearance of green, blue, and purple tattoo inks - often the colors most ... Medicine (LSM), the official journal of the American Society for Laser Medicine and Surgery, ...
(Date:9/12/2018)... ... September 12, 2018 , ... ... education, is pleased to support the professional development of academic librarians by sponsoring ... , The entrants were asked to submit successful strategies to increase collaboration among ...
(Date:9/7/2018)... (PRWEB) , ... September 06, 2018 , ... ... Amedica Corporation (NASDAQ: AMDA) to purchase its commercial spine business, which includes its ... directly related to the spine that result from it. The deal will make ...
Breaking Biology News(10 mins):
(Date:9/12/2018)... and VIENNA, Austria (PRWEB) , ... September 10, 2018 , ... ... supplier of Semantic Graph Database technology, AllegroGraph , for Knowledge Graphs, and ... provider of Semantic AI solutions, today announced a partnership to develop the Noam ...
(Date:9/7/2018)... ... September 06, 2018 , ... ... 25th-28th is a meeting of “The industry’s preeminent event on novel drug targets.” ... scientists powerful tools to study these emerging targets in a quest to find ...
(Date:8/31/2018)... ... August 29, 2018 , ... A recent ... of Southampton and the Institute of Industrial Science, the University of Tokyo, demonstrated ... accelerate the exploration and study of hard to reach deep sea ecosystems, like ...
(Date:8/29/2018)... ... August 28, 2018 , ... ... the results of a safety study performed on an allogeneic (donor derived) stem ... Regenerative Medicine Association (NAVRMA) conference in September. He is also the organizer ...
Breaking Biology Technology: