"Long before it's in the papers"
August 17, 2009

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Cancer stem cells not drug-immune, researchers find

Aug. 13, 2009
Courtesy Cell Press
and World Science staff

So-called “can­cer stems cells”—cells that spawn ma­lig­nant growths while re­sisting stand­ard can­cer treat­ments—aren’t as in­de­struct­ible as they were widely thought to be, ac­cord­ing to a new stu­dy.

In the lab­o­r­a­to­ry re­search, sci­en­tists said, they found the first chem­i­cal that tar­gets can­cer stem cells spe­cif­ic­ally, leav­ing oth­er cells un­harmed.

Piyush Gupta of the Mas­sa­chu­setts In­sti­tute of Tech­nol­o­gy and col­leagues said they de­vel­oped a high-efficiency screen­ing meth­od that let them sys­tem­at­ic­ally search for drugs that kill can­cer stem cells. 

They then screened 16,000 nat­u­ral and com­mer­cial chem­i­cal com­pounds for their abil­ity to kill only cells with prop­ert­ies like those of cancer stem cells. That screen turned up 32 con­tenders.

The re­search­ers then nar­rowed that list to a hand­ful of com­pounds that they could readily get in suf­fi­cient quanti­ties for fur­ther test­ing on nor­mal can­cer stem cells. Of those, one called sali­no­mycin was dubbed the clear win­ner.

Sali­no­mycin was found to slash the pro­por­tion of breast can­cer stem cells more than 100-fold com­pared to a com­monly used chemoth­erapy drug for breast can­cer called pa­cli­taxel, or Taxol. Sali­no­mycin-treated cells were al­so less able than pa­cli­taxel-treated ones to seed tu­mors when in­jected in­to mice, the re­search­ers said. Sali­no­mycin treat­ment al­so was not­ed to slow the growth of the an­i­mals’ tu­mors.

The re­search­ers con­ducted the in­i­tial tests on cell sam­ples that had been ma­ni­pu­lated to in­crease the num­ber of those with the stem-like prop­er­ties, in­clud­ing in­creased re­sistance to stand­ard can­cer drugs. That meas­ure was tak­en in or­der to make detecta­ble re­sults pos­si­ble, the sci­en­tists ex­plained.

It re­mains un­clear wheth­er sali­no­mycin it­self might find its way to clin­i­cal use, Gupta said, but more general­ly, the find­ings high­light a new av­e­nue for the de­vel­op­ment of can­cer ther­a­pies. 

“To date, ra­tional can­cer ther­a­pies have been de­signed to tar­get spe­cif­ic” muta­t­ions in tu­mors, the re­search­ers wrote, re­port­ing their find­ings in the Aug. 13 on­line is­sue of the re­search jour­nal Cell. 

“The find­ings here in­di­cate that a sec­ond ap­proach may al­so prove use­ful—namely, search­ing for agents that tar­get spe­cif­ic states of can­cer cell dif­fer­entia­t­ion,” or stage of de­vel­op­ment. Can­cer stem cells are an im­ma­ture form of can­cerous cell. “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,” they added.

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So-called “cancer stems cells”—cells that spawn malignant growths and resist standard treatments—aren’t as indestructible as they were widely thought to be, according to a new study. In the laboratory research, scientists said, they found the first chemical that targets cancer stem cells specifically, leaving others unharmed. Piyush Gupta of the Massachusetts Institute of Technology and colleagues said they developed a high-efficiency screening method that let them systematically search for drugs that kill cancer stem cells. They then screened 16,000 natural and commercial chemical compounds for their ability to kill those stem-like cells and not other cancer cells among samples of breast cancer cells. That screen turned up 32 contenders. The researchers then narrowed that list to a handful of compounds that they could readily get in sufficient quantities for further testing on normal cancer stem cells. Of those, one called salinomycin was dubbed the clear winner. Salinomycin was found to slash the proportion of breast cancer stem cells more than 100-fold compared to a commonly used chemotherapy drug for breast cancer called paclitaxel, or Taxol. Salinomycin-treated cells were also less able than paclitaxel-treated ones to seed tumors when injected into mice, the researchers said. Salinomycin treatment also was noted to slow the growth of the animals’ tumors. The researchers conducted the initial tests on cell samples that had been manipulated to increase the number of those with the stem-like properties, including increased resistance to standard cancer drugs. That measure was taken in order to make detectable results possible, the scientists explained. It remains unclear whether salinomycin itself might find its way to clinical use, Gupta said, but more generally, the findings highlight a new avenue for the development of cancer therapies. “To date, rational cancer therapies have been designed to target specific” mutations in tumors, the researchers wrote, reporting their findings in the Aug. 13 online issue of the research journal Cell. “The findings here indicate that a second approach may also prove useful—namely, searching for agents that target specific states of cancer cell differentiation,” or stage of development. Cancer stem cells are an immature form of cancerous cell. “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,” they added.