Researchers discover gene that permanently stops cancer cell proliferation

August 1, 2012

Researchers at Case Western Reserve University School of Medicine have discovered a mutant form of the gene, Chk1, that when expressed in cancer cells, permanently stopped their proliferation and caused cell death without the addition of any chemotherapeutic drugs. This study illustrates an unprecedented finding, that artificially activating Chk1 alone is sufficient to kill cancer cells.

"We have identified a new direction for cancer therapy and the new direction is leading us to a reduction in toxicity in cancer therapy, compared with chemotherapy or radiation therapy," said Dr. Zhang, assistant professor, Department of Pharmacology at the School of Medicine, and member of the university's Case Comprehensive Cancer Center. "With this discovery, scientists could stop the proliferation of , allowing physicians time to fix cells and ."

While studying the basic mechanisms for genome integrity, Dr. Zhang's team unexpectedly discovered an active mutant form of human Chk1, which is also a non-natural form of this gene. This mutation changed the protein conformation of Chk1 from the inactive form into an active form. Remarkably, the research team discovered that when expressed in cancer cells, this active mutant form of Chk1 permanently stopped cancer and caused cell death in even without the addition of any .

The biggest advantage of this potential strategy is that no toxic chemotherapeutic drug is needed to achieve the same cancer killing effect used with a combination of Chk1 inhibitors and chemotherapeutic drugs.

Cells respond to by activating networks of signaling pathways, termed cell cycle checkpoints. Central to these genome pathways is the protein kinase, called Chk1. Chk1 facilitates cell survival, including cancer cells, under stressful conditions, such as those induced by chemotherapeutic agents, by placing a temporary stop on the cell cycle progression and coordinating repair programs to fix the DNA errors.

It has long been suggested that combining Chk1 inhibition with chemotherapy or radiotherapy should significantly enhance the anticancer effect of these therapies. This idea has serves as the basis for multiple pharmaceutical companies searching for potential Chk1 inhibitors that can effectively combine with chemotherapy in cancer therapy. To date, no Chk1 inhibitor has passed the clinical trial stage III . This led Dr. Zhang's team to look for alternative strategies for targeting Chk1 in .

Future research by Dr. Zhang and his team will consider two possible approaches to artificially activating Chk1 in cancer cells. One possibility is to use the gene therapy concept to deliver the active mutant form of Chk1 that the team discovered, into cancer cells. The other is to search for small molecules that can induce the same conformational change of Chk1, so that they can be delivered into cancer cells to activate Chk1 molecules. The consequence of either would be permanent cell proliferation inhibition and cancer.

This study is published in Cancer Research.

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7 comments

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h20dr
5 / 5 (4) Aug 01, 2012
Wow, this is great news if they truly succeed.
Rahvasaadik
3 / 5 (2) Aug 01, 2012
The mutant form of gene Chk1 works, because it's the cells' CHKDSK utility, which repairs file system errors.
dogbert
5 / 5 (1) Aug 01, 2012
Excellent. Another pathway to use to fight cancer.

I wonder if activating Chk1 would also work on the underlying stem cell precursors to the cancer.
wealthychef
not rated yet Aug 01, 2012
Sure makes it sound like a cure is right around the corner, right? NOT. Progress i medicine seems so fast on one hand, and so slow on the other -- hurry! We need to hit Aubrey De Grey's escape velocity!
Singularity24601
not rated yet Aug 02, 2012
Yet another potential target for cancer therapies, but not an obvious treatment breakthrough or cure by any means. The challenge is not about how to permanently disable or kill cancer cells (we've actually been able to do this for decades), but rather how to ensure that such treatment works on the whole population of cancer cells, rather than sparing a handful of viable resistant variants, resulting in incurability via natural selection.
tkjtkj
not rated yet Aug 02, 2012
Readers should keep in mind that cancer itself *might* be an abherrent result of a totally natural (and necessary!) cell process that is protective: ie, as in 'auto-killing' cells who've 'gone wrong' .. This article's suggestion that a gene can turn OFF cancer cells' reproduction might very wello have the consequences of also turning 'off' any natural and beneficial 'programmed cell suicide' function!!
This could turn out to be an unmitigated disaster .. and such possibilities are exacly WHY much more research needs to be done. Haste could theoretically cause the biggest 'waste' of human life imaginable!
tkjtkj@gmail, m.d.
Infinion
5 / 5 (1) Aug 08, 2012
Readers should keep in mind that cancer itself *might* be an abherrent result of a totally natural (and necessary!) cell process that is protective: ie, as in 'auto-killing' cells who've 'gone wrong' .. This article's suggestion that a gene can turn OFF cancer cells' reproduction might very wello have the consequences of also turning 'off' any natural and beneficial 'programmed cell suicide' function!!
This could turn out to be an unmitigated disaster .. and such possibilities are exacly WHY much more research needs to be done. Haste could theoretically cause the biggest 'waste' of human life imaginable!
tkjtkj@gmail, m.d.


how about we let the cancer patients make that decision

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