First compound that selectively kills ‘invincible’ cancer stem cells discovered

August 14, 2009

(ChattahBox) — Deadly cancer stem cells that drive tumor growth but have proven to be resistant to both radiation and chemotherapy treatments, have been killed off for the first time. But it was revealed yesterday that the first chemical compound to wipe them out had been found. 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 Taxolâ„¢). 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.

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The researchers include Piyush B. Gupta, Massachusetts Institute of Technology, Cambridge, MA, Broad Institute of MIT and Harvard, Cambridge, MA; Tamer T. Onder, Massachusetts Institute of Technology, Cambridge, MA, Whitehead Institute for Biomedical Research, Cambridge, MA; Guozhi Jiang, Massachusetts Institute of Technology, Cambridge, MA, Broad Institute of MIT and Harvard, Cambridge, MA; Kai Tao, Tufts Medical Center, Boston, MA; Charlotte Kuperwasser, Tufts Medical Center, Boston, MA; Robert A. Weinberg, Massachusetts Institute of Technology, Cambridge, MA, Whitehead Institute for Biomedical Research, Cambridge, MA, MIT Ludwig Center for Molecular Oncology, Cambridge, MA; and Eric S. Lander, Massachusetts Institute of Technology, Cambridge, MA, Whitehead Institute for Biomedical Research, Cambridge, MA, Broad Institute of MIT and Harvard, Cambridge, MA, Harvard Medical School, Boston, MA.


Comments

2 Responses to “First compound that selectively kills ‘invincible’ cancer stem cells discovered”

  1. Brick Paving on August 14th, 2009 9:15 pm

    This can be considered a major breakthrough in cancer research. Salinomycin may prove to be “it”. I think it was in 1997 that the first conclusive evidence for CSCs was published . At the heart of every tumor, some researchers believe, lie a handful of aberrant stem cells that maintain the malignant tissue. Now comes this chemical to kill them off. Thanks for sharing this wonderful news.

  2. Stem cells on August 17th, 2009 5:33 am

    A compound has been discovered that targets specific master cells that aid in the proliferation of breast cancer cells. Salinomycin outperformed other drugs by being hundred times more effective at destroying the cells in a test tube.

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