Researchers Studying Model to Learn Why Certain Cancers Become Resistant to Drugs

Sep 21, 2007

Resistance to chemotherapy treatments can be the worst news a cancer patient ever receives. A pair of researchers at the University of Missouri-Columbia is working steadfastly to learn why some tumors eventually build a tolerance to the common chemotherapy drug cisplatin, in hopes of identifying the particular genes that can be manipulated to make treatment as effective as possible.

In a paper published in the latest edition of Proceedings of the National Academy of Sciences, Hannah and Stephen Alexander, professors of biological sciences in MU's College of Arts and Science, in collaboration with Gad Shaulsky and Adam Kuspa, professors at the Baylor School of Medicine, demonstrate that a model organism called "Dictyostelium discoideum" is useful for studying mechanisms of cisplatin drug sensitivity.

Dictyostelium discoideum cells share many genes and biochemistry with human cells - there are more than 30,000 genes in one human cell compared with 15,000 in Dictyostelium discoideum - which simplifies the process of isolating and studying particular genes. The current study identified 400 genes that have the potential for use in improving cisplatin therapy.

"The basic issue is that many types of cancer are treated with cisplatin," Stephen Alexander said. "In some cases it's the best drug, and in some cases it's the only drug. Nevertheless, lots of cancers are either resistant to it or become resistant during treatment. There's a lot of work being done in developing new drugs as cancer therapies, but not many of them have come on the market yet. Since cisplatin is effective and has already been approved, why not try to make it better?"

During more than eight years of research, the Alexanders have examined why tumors become resistant to cisplatin and what, if any, biochemical pathways can be used to improve the drug's efficiency. They identified genes for sphingolipid metabolism as key to whether a tumor cell lives or dies after treatment with cisplatin. The current collaboration with the Baylor team has greatly expanded these studies.

Shaulsky and Kuspa have developed microarray technologies to determine the patterns of gene expression in Dictyostelium discoideum and detect the effects of treatments. Together, the teams of researchers embarked to find the global response to cisplatin and how mutants in sphingolipid metabolism resistant to cisplatin affected the response. The study established that the cause of resistance is not simply that cells do not take up the drug or that the drug is neutralized, but that a specific set of genes responds uniquely to the treatment. Finding ways to use those genes to increase sensitivity to cisplatin could lead to more effective therapy.

"We used genetics to find genes that are involved, and we discovered several completely novel pathways that no one had ever thought was involved with this," Stephen Alexander said. "Ultimately, we¿re looking for a way to make cisplatin more effective, and the idea is to find out what's going on in the cell that determines whether cells are sensitive or not, and to boost some pathway to make it better."

Source: University of Missouri

Explore further: Discovery could lead to new cancer treatment

add to favorites email to friend print save as pdf

Related Stories

New fusion gene plays role in some stomach cancers

Apr 06, 2011

A newly discovered hybrid gene appears to play a direct role in some stomach cancers, according to an international team of scientists led by researchers at Duke-NUS Graduate Medical School Singapore.

Scientists ID new cancer drug target

Nov 08, 2010

Suppressing cancer cells' ability to replicate damaged DNA could dramatically enhance the effectiveness of chemotherapy drugs such as cisplatin, according to a new pair of papers from MIT biologists.

Micro-RNA determines malignancy of lung cancer

Sep 08, 2010

A small RNA molecule determines whether or not lung cancer cells grow invasively and metastasize. This has been discovered in the culture dish by scientists of the German Cancer Research Center and the University Medical ...

Recommended for you

Discovery could lead to new cancer treatment

15 hours ago

A team of scientists from the University of Colorado School of Medicine has reported the breakthrough discovery of a process to expand production of stem cells used to treat cancer patients. These findings could have implications ...

Is the HPV vaccine necessary?

21 hours ago

As the school year starts in full swing many parents wonder if their child should receive the HPV vaccine, which is recommended for girls ages 11-26 and boys 11-21. There are a lot of questions and controversy around this ...

User comments : 0