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

September 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: Researchers study the cancer cell genes that resist drugs

Related Stories

Researchers study the cancer cell genes that resist drugs

September 25, 2017
Researchers from the People's Friendship University of Russia (RUDN University) have studied the mechanism of drug resistance for ovarian and breast cancer cells. They discovered that these cancer cells have a redox-dependent ...

Personalised cancer treatment

September 4, 2017
In Norway, more and more people are being affected by cancer of the mouth and throat. In recent years, the incidence has increased but the mortality has remained the same. Cisplatin is one of the most commonly administered ...

Preventing childhood deafness following chemotherapy treatment

September 12, 2017
Charity Action on Hearing Loss is supporting the biotechnology firm Otomagnetics, which today announces an important breakthrough towards preventing hearing loss caused by a widely used chemotherapy drug.

New biomarker for common lung cancer predicts responses to chemotherapy

July 26, 2012
Patients with the most common type of lung cancer are notoriously insensitive to chemotherapy drugs, including cisplatin. New findings related to the cellular pathways that regulate responses to cisplatin have now been published ...

Inherited gene variations tied to treatment-related hearing loss in cancer patients

February 9, 2015
St. Jude Children's Research Hospital investigators have discovered inherited genetic variations that are associated with rapid hearing loss in young cancer patients treated with the drug cisplatin. The research appears in ...

Newer cancer drug may help protect kidneys from damage caused by older drug

December 15, 2015
A class of drugs used increasingly to help fight cancer may have the additional benefit of protecting the kidneys when packaged with the powerful chemotherapy agent cisplatin.

Recommended for you

CAR-T immunotherapy may help blood cancer patients who don't respond to standard treatments

October 20, 2017
Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis is one of the first centers nationwide to offer a new immunotherapy that targets certain blood cancers. Newly approved ...

Researchers pinpoint causes for spike in breast cancer genetic testing

October 20, 2017
A sharp rise in the number of women seeking BRCA genetic testing to evaluate their risk of developing breast cancer was driven by multiple factors, including celebrity endorsement, according to researchers at the University ...

Study shows how nerves drive prostate cancer

October 19, 2017
In a study in today's issue of Science, researchers at Albert Einstein College of Medicine, part of Montefiore Medicine, report that certain nerves sustain prostate cancer growth by triggering a switch that causes tumor vessels ...

Gene circuit switches on inside cancer cells, triggers immune attack

October 19, 2017
Researchers at MIT have developed a synthetic gene circuit that triggers the body's immune system to attack cancers when it detects signs of the disease.

One to 10 mutations are needed to drive cancer, scientists find

October 19, 2017
For the first time, scientists have provided unbiased estimates of the number of mutations needed for cancers to develop, in a study of more than 7,500 tumours across 29 cancer types. Researchers from the Wellcome Trust Sanger ...

Researchers target undruggable cancers

October 19, 2017
A new approach to targeting key cancer-linked proteins, thought to be 'undruggable," has been discovered through an alliance between industry and academia.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.