Blocking DNA repair protein likely to make cancer therapy saferJune 2nd, 2010 - 5:25 pm ICT by ANI
Washington, June 2 (ANI): Blocking DNA repair protein could lead to targeted, safer cancer therapy, according to a new American research.
The study, conducted by researchers at the University of Pittsburgh Cancer Institute (UPCI) and the School of Medicine, has appeared in Science Signaling.
The work provides new insights into mechanisms of how the body fixes environmentally induced DNA damage and into the deadly neurological disease ataxia-telangiectasia (A-T), said senior author Christopher Bakkenist, assistant professor of radiation oncology, pharmacology and chemical biology at UPCI and the School of Medicine.
He said: “A characteristic symptom of A-T is heightened sensitivity to ionizing radiation, such as X-rays and gamma rays.
“If we understand why that happens, then we might be able to reproduce it to make tumor cells vulnerable to radiation treatments while sparing healthy cells, which would make therapy more effective while minimizing side effects.”
In A-T, brain areas that control movement progressively degenerate, causing walking and balance problems.
Patients carry a gene mutation that stops production of a protein called ATM kinase, which spurs other proteins involved in normal cell division, DNA repair and cell death.
Radiation causes DNA mutations during the process of cell division, when genetic material is copied for a new cell to form.
The cell has repair pathways that include checkpoints to look for errors as well as methods to repair them, but if enough mutations accumulate, the cell could become cancerous or self-destruct.
A-T patients, who lack the kinase, have a higher risk for developing cancer, Dr. Bakkenist said.
He and his colleagues tested what would happen if they blocked the activity of ATM kinase in cells that make the protein.
They had already determined that administering an ATM kinase inhibitor from 15 minutes to 75 minutes after radiation exposure was sufficient to make normal cells more sensitive to the effects of radiation.
To their surprise, they found that inactivation of ATM kinase prevented a type of DNA repair that is essential for proper duplication of genetic material during replication.
However, A-T cells did not have this problem despite lacking the kinase; they presumably use another method to check for and correct those errors.
The discovery revealed a new approach to target cancer.
Dr. Bakkenist explained: “A characteristic of tumor cells is that they rapidly replicate, possibly because they have mutations that encourage cell division or that thwart repair pathways.
“But ATM kinase remains present in the vast majority of human cancers, so that suggests it is needed by those diseased cells during replication.”
Cells that, unlike cancer cells, are not going through what’s known as replication stress, would not be affected by an ATM inhibitor and, like A-T cells, likely have another way of repairing certain radiation-induced mutations, he said.
Dr. Bakkenist said: “So that would make cancer cells particularly vulnerable to an ATM inhibitor, while healthy cells should be unaffected.” (ANI)
- Ultraviolet light 'helps skin cancer cells survive, proliferate' - Dec 08, 2010
- Soy 'ups radiation's ability to destroy lung cancer cells' - Apr 02, 2011
- Enzyme crucial to DNA replication may be potent anti-cancer drug target - Apr 15, 2011
- Overabundance of protein promotes growth of breast cancer stem cells - Feb 16, 2011
- 'Chaperone' enzyme could help cells tolerate cancer-causing DNA damage - Jan 19, 2011
- DNA discovery paves way for new therapies for hereditary cancers - Jul 09, 2010
- Novel therapy may eradicate lung cancer - Oct 30, 2009
- Gene that prevents stem cells from turning cancerous identified - Oct 15, 2010
- Possible new treatment strategies for pancreatic cancer found - Mar 04, 2011
- How skin cells turn cancerous in sunlight - Jan 16, 2010
- Restoring gene may slow spread of advanced lung tumours - Nov 25, 2010
- Sporadic breast cancers linked to ineffective DNA repair systems - Nov 30, 2010
- Key pathway implicated in progression of childhood cancer found - Sep 19, 2010
- 'Guardian' protein prevents DNA damage during replication - Aug 02, 2010
- Wonder drug could kill all types of cancer - Jun 27, 2011
Tags: balance problems, brain areas, cancer therapy, characteristic symptom, chemical biology, disease ataxia telangiectasia, dna damage, dna mutations, dna repair, gamma rays, gene mutation, ionizing radiation, neurological disease, new insights, pittsburgh cancer institute, radiation exposure, radiation oncology, radiation treatments, tumor cells, upci