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First compound that specifically kills cancer stem cells found
August 14, 2009The cancer stem cells that drive tumor growth and resist chemotherapies and radiation treatments that kill other cancer cells aren't invincible after all. Researchers reporting online on August 13th in the journal Cell, a Cell Press publication, have discovered the first compound that targets those cancer stem cells directly.
"It wasn't clear it would be possible to find compounds that selectively kill cancer stem cells," said Piyush Gupta of the Massachusetts Institute of Technology (MIT) and the Broad Institute. "We've shown it can be done."
The team including MIT's Robert Weinberg and the Broad Institute's Eric Lander developed a new high-throughput screening method that makes it possible for the first time to systematically look for agents that kill cancer stem cells. That ability had previously eluded researchers due to the rarity of those cells within tumor cell populations and their relative instability in laboratory culture.
In the new study, the researchers manipulated cultured breast cancer cells to greatly enrich for those with the stem-like properties, including increased resistance to standard cancer drugs. They then screened a library of 16,000 natural and commercial chemical compounds for their ability to kill those stem-like cells and not other cancer cells. That screen turned up 32 contenders.
The researchers narrowed that list down to a handful of chemicals that they could readily get in sufficient quantities for further testing on normal cancer stem cells. Of those, one called salinomycin was the clear winner.
Salinomycin reduced the proportion of breast cancer stem cells by more than 100-fold compared to a commonly used chemotherapeutic drug for breast cancer called paclitaxel (aka Taxol™). Salinomycin-treated cells were less able than paclitaxel-treated ones to seed tumors when injected into mice, they report. Salinomycin treatment also slowed the growth of the animals' tumors.
Studies of salinomycin-treated human breast tumors also showed a loss in the activity of genes associated with cancer stem cells.
Exactly how salinomycin's works against cancer stem cells, the researchers don't yet know. As its name suggests, the chemical has antibiotic properties that likely aren't relevant to its newfound cancer stem cell-killing ability. It also disturbs cells' potassium balance.
It remains unclear whether salinomycin itself might find its way to the clinic, Gupta said, since many pharmaceutical steps are involved in the drug discovery process. Nevertheless, the chemical does serve as an immediate tool for manipulating cancer stem cell numbers and observing the effects on cancer's spread and progression.
The findings also highlight a new avenue for the development of cancer therapies, the researchers say.
" To date, rational cancer therapies have been designed to target specific genetic alterations present within tumors," they wrote. "The findings here indicate that a second approach may also prove useful-namely, searching for agents that target specific states of cancer cell differentiation. Accordingly, future therapies could offer greater possibilities for individualized treatment by considering both the genetic alterations and differentiation states present within the cancer cells of a tumor at the time of diagnosis."
They envision a future in which combination therapies might couple more traditional cancer drugs with those designed to hit the cancer stem cells that would otherwise get left behind.
Cell Press
In the new study, the researchers manipulated cultured breast cancer cells to greatly enrich for those with the stem-like properties, including increased resistance to standard cancer drugs. They then screened a library of 16,000 natural and commercial chemical compounds for their ability to kill those stem-like cells and not other cancer cells. That screen turned up 32 contenders.
The researchers narrowed that list down to a handful of chemicals that they could readily get in sufficient quantities for further testing on normal cancer stem cells. Of those, one called salinomycin was the clear winner.
Salinomycin reduced the proportion of breast cancer stem cells by more than 100-fold compared to a commonly used chemotherapeutic drug for breast cancer called paclitaxel (aka Taxol™). Salinomycin-treated cells were less able than paclitaxel-treated ones to seed tumors when injected into mice, they report. Salinomycin treatment also slowed the growth of the animals' tumors.
Studies of salinomycin-treated human breast tumors also showed a loss in the activity of genes associated with cancer stem cells.
Exactly how salinomycin's works against cancer stem cells, the researchers don't yet know. As its name suggests, the chemical has antibiotic properties that likely aren't relevant to its newfound cancer stem cell-killing ability. It also disturbs cells' potassium balance.
It remains unclear whether salinomycin itself might find its way to the clinic, Gupta said, since many pharmaceutical steps are involved in the drug discovery process. Nevertheless, the chemical does serve as an immediate tool for manipulating cancer stem cell numbers and observing the effects on cancer's spread and progression.
The findings also highlight a new avenue for the development of cancer therapies, the researchers say.
" To date, rational cancer therapies have been designed to target specific genetic alterations present within tumors," they wrote. "The findings here indicate that a second approach may also prove useful-namely, searching for agents that target specific states of cancer cell differentiation. Accordingly, future therapies could offer greater possibilities for individualized treatment by considering both the genetic alterations and differentiation states present within the cancer cells of a tumor at the time of diagnosis."
They envision a future in which combination therapies might couple more traditional cancer drugs with those designed to hit the cancer stem cells that would otherwise get left behind.
Cell Press
Cancer Stem Cells Current Events and Cancer Stem Cells News RSSGovernor recognizes stem cell research at Einstein
Albert Einstein College of Medicine of Yeshiva University hosted a roundtable discussion on stem cell research with New York Governor David A. Paterson today.
MDC scientists show how hematopoietic stem cell development is regulated
During cell division, whether hematopoietic stem cells (HSCs) will develop into new stem cells (self-renewal) or differentiate into other blood cells depends on a chemical process called DNA methylation.
Echoes of phlogiston in stem cell biology
Before it was learned that matter burns by taking up oxygen, most chemists sought to explain combustion as the release of a mysterious substance, which they named "phlogiston".
Penn State College of Medicine research isolates liver cancer stem cells prior to tumor formation
Penn State College of Medicine researchers, in collaboration with colleagues at the University of Southern California, have taken an important step in understanding the role of stem cells in development of liver cancer.
Diabetes drug kills cancer stem cells in combination treatment in mice
In a one-two punch, a familiar diabetes drug reduced tumors faster and prolonged remission in mice longer than chemotherapy alone by targeting cancer stem cells, Harvard Medical School researchers reported in the September 14 online first edition of Cancer Research, a journal of the American Association for Cancer Research.
Turning back the clock: Fasting prolongs reproductive life span
Scientific dogma has long asserted that females are born with their entire lifetime's supply of eggs, and once they're gone, they're gone.
STAT3 Gene Regulates Cancer Stem Cells in Brain Cancer
In a study published online in advance of print in Stem Cells, Tufts researchers report that the STAT3 gene regulates cancer stem cells in brain cancer. Cancer stem cells have many characteristics of stem cells and are thought to be the cells that drive tumor formation.
Stripping leukemia-initiating cells of their 'invisibility cloak'
Two new studies reveal a way to increase the body's appetite for gobbling up the cancer stem cells responsible for acute myeloid leukemia (AML), a form of cancer with a particularly poor survival rate.
Toronto researcher's discovery points to a new treatment avenue for acute myeloid leukemia
Dr. John Dick, Senior Scientist at the Ontario Cancer Institute, the research arm of Princess Margaret Hospital, co-led a multinational team that has developed the first leukemia therapy that targets a protein, CD123, on the surface of cancer stem cells that drive acute myeloid leukemia (AML), which is an aggressive disease with a poor outcome.
Neural stem cell differentiation factor discovered
Neural stem cells represent the cellular backup of our brain. These cells are capable of self-renewal to form new stem cells or differentiate into neurons, astrocytes or oligodendrocytes.
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