Hopkins Researchers Discover Key Target In Molecular Pathway That Initiates Colon Cancer

September 04, 1998

In the latest of a series of discoveries about colon cancer genes, researchers at the Johns Hopkins Oncology Center and the Howard Hughes Medical Institute have discovered a connection between two of them, APC and c-MYC, that conspires to initiate almost all colon cancers. Their findings are reported in the September 4, 1998, issue of SCIENCE.

The APC tumor suppressor gene, which acts like a brake on cell growth, loses that ability when mutated. The c-MYC gene has long been known as an oncogene, a type of gene that promotes cancer cell growth. Now, Hopkins scientists Bert Vogelstein, M.D., and Kenneth W. Kinzler, Ph.D., have found that the mutated APC gene controls the expression of c-MYC activation. APC was first identified and linked to colon cancer in 1991 by research teams including those led by Vogelstein and Kinzler.

Every person carries the c-MYC oncogene, but it remains under control in the colon until APC inactivation awakens it, generating the distinctive uncontrolled cell growth that mark cancers. "Cancer is like a car with the accelerator pushed to the floor and failing brakes," says Vogelstein, professor of oncology at Hopkins and a Hughes scholar.

"In this case, c-MYC is the accelerator and APC is the failed brakes," he explains. When suppressor genes, like APC, malfunction either through heredity or as a result of exposure to carcinogens, cells get signals to continue multiplying until they are out of control. "Now we know that in colon cancer a mutated APC gene signals to c-MYC," Vogelstein says.

The new findings about the APC pathway and how it functions may suggest potential new drug strategies that could prevent colon cancer by blocking the signal that activates c-MYC, says Kinzler, associate professor of oncology and director of the study. "Just eight years ago, we didn't even know about APC mutations. Now, we know this type of mutation is one of the earliest genetic changes in most colon cancers, and we know what it does to c-MYC. It's like a jigsaw puzzle. We have identified individual pieces of the cancer puzzle and now we can begin to put them together to see the whole picture of how they work together to cause cancer," Kinzler says. Colon cancer, among the most common cancers in both men and women, this year will strike more than 131,000 Americans. Some 56,500 individuals will die of it.

In addition to Vogelstein and Kinzler, other research participants included Tong-Chuan He, M.D., Ph.D., Andrew B. Sparks, Ph.D., Carlo Rago, B.S., Heiko Hermeking, Ph.D., Leigh Zawel, Ph.D., Luis T. Da Costa, M.S., and Patrice J. Morin, Ph.D. The study was funded by the National Institutes of Health.
Under a licensing agreement between the Johns Hopkins University and Genzyme, SAGE technology, which was used this study, is licensed to Genzyme for commercial purposes. Kenneth W. Kinzler, Ph.D., and Bert Vogelstein, M.D., are entitled to a share of the royalty received by the University from sales of the licensed technology. The SAGE technology is freely available to academia for research purposes. Kinzler and Vogelstein are consultants to Genzyme. The University and the researchers own Genzyme stock, which is subject to certain restrictions under University policy. The terms of this arrangement are being managed by the University in accordance with its conflict of interest policies.

Johns Hopkins Medicine

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.