Different drug combinations work best for prevention versus treatment of colorectal tumors

April 7, 2013

Colorectal cancer is the second leading cause of cancer-related deaths in the United States. Once colorectal cancer has spread to other parts of the body, only 11 percent of patients will survive five years from the date of their diagnosis. Most colorectal cancers are adenocarcinomas—cancers that begin in cells that make and release mucus and other fluids. Adenocarcinomas begin as benign tumors called adenomas, which become malignant over time. By treating adenomas before they become cancerous, it could be possible to prevent colorectal cancer.

Researchers at Fox Chase Cancer Center have tested the effectiveness of two in preventing and treating colorectal adenomas in . A team led by Wen-Chi Chang, PhD, assistant research professor at Fox Chase, found that the effect of these drugs, which have already been approved by the for the treatment of other conditions, depends on whether adenomas are present when drug treatment begins. Chang will present these findings at the AACR Annual Meeting 2013 on Sunday, April 7.

"We often get focused on either the preventive or therapeutic setting and don't think about how these drugs are maybe serving more than one purpose," says senior author on the study Margie L. Clapper, PhD, co-leader of the Cancer Prevention and Control Program at Fox Chase. "The most exciting thing for us was to be able to track these tumors and for the first time distinguish between prevention and chemotherapy, and to show that one agent is maybe effective in both settings if used appropriately, or in this case, in combination with another agent."

Past studies in animals have shown that colorectal tumors can be suppressed by combined treatment with two drugs: a non-steroidal anti-inflammatory compound called sulindac and a cholesterol-lowering medication called —whose brand name is Lipitor. But in those studies, tumors were induced in an unnatural way—through exposure to —whereas in humans, cancer often has genetic origins.

To evaluate the effectiveness of sulindac and atorvastatin in an animal model more relevant to humans, Chang, Clapper and their colleagues used a unique mouse that had genetic alterations that cause them to develop multiple colorectal adenomas, without exposure to carcinogens. "No one had previously tested the effectiveness of this drug combination against colorectal cancer originating from alterations in the genome," Clapper says. "In some ways, using this type of preclinical tumor model represents a new paradigm for doing prevention studies and therapeutic studies."

In the new study, the researchers treated the mice with either drug alone or in combination for 100 days and used colonoscopic examinations to evaluate the presence and size of tumors before and after treatment. In mice that had tumors prior to treatment, only combination therapy reduced the number of adenomas in the colon by the end of the treatment period.

The results were strikingly different in mice that were tumor-free when treatment began. In these mice, exposure to atorvastatin alone or in combination with sulindac resulted in about a three-fold increase in the percentage of mice that were tumor-free by the end of the treatment period. Among these mice, 44 percent of those treated with atorvastatin alone and 30 percent of those treated with both drugs did not develop tumors, compared with 13 percent of mice that received no treatment and nine percent that received sulindac alone. Moreover, atorvastatin treatment completely inhibited the formation of microscopic adenomas in these mice.

The findings demonstrate that the effectiveness of the two drugs at preventing and treating colorectal depends on whether tumors are present prior to the onset of treatment. "Based on this study, we're able to say that if you don't have a tumor to begin with, maybe Lipitor is best, but if you do have a to begin with, you need the combination therapy," Chang says. "We can start to tailor clinical care based upon the disease state as well as the establishment of tumors."

Moving forward, the researchers plan to study the specific genetic alterations in this particular mouse model, with the goal of identifying molecular pathways that could be targeted with therapies.

Explore further: Researchers uncover a viable way for colorectal cancer patients to overcome drug resistance

Related Stories

Researchers uncover a viable way for colorectal cancer patients to overcome drug resistance

April 4, 2012
When combined with other treatments, the drug cetuximab—which works by slowing or stopping the growth of cancer cells—has been shown to extend survival in certain types of cancer, including metastatic colorectal ...

Inflammatory mediator promotes colorectal cancer by stifling protective genes

January 22, 2012
Chronic inflammation combines with DNA methylation, a process that shuts down cancer-fighting genes, to promote development of colorectal cancer, scientists at The University of Texas MD Anderson Cancer Center report today ...

Recommended for you

Stem cell therapy attacks cancer by targeting unique tissue stiffness

July 26, 2017
A stem cell-based method created by University of California, Irvine scientists can selectively target and kill cancerous tissue while preventing some of the toxic side effects of chemotherapy by treating the disease in a ...

Understanding cell segregation mechanisms that help prevent cancer spread

July 26, 2017
Scientists have uncovered how cells are kept in the right place as the body develops, which may shed light on what causes invasive cancer cells to migrate.

Study uncovers potential 'silver bullet' for preventing and treating colon cancer

July 26, 2017
In preclinical experiments, researchers at VCU Massey Cancer Center have uncovered a new way in which colon cancer develops, as well as a potential "silver bullet" for preventing and treating it. The findings may extend to ...

Compound shows promise in treating melanoma

July 26, 2017
While past attempts to treat melanoma failed to meet expectations, an international team of researchers are hopeful that a compound they tested on both mice and on human cells in a petri dish takes a positive step toward ...

Study may explain failure of retinoic acid trials against breast cancer

July 25, 2017
Estrogen-positive breast cancers are often treated with anti-estrogen therapies. But about half of these cancers contain a subpopulation of cells marked by the protein cytokeratin 5 (CK5), which resists treatment—and breast ...

Breaking the genetic resistance of lung cancer and melanoma

July 25, 2017
Researchers from Monash University and the Memorial Sloan Kettering Cancer Center (MSKCC, New York) have discovered why some cancers – particularly lung cancer and melanoma – are able to quickly develop deadly resistance ...

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.