Researchers: 'Exciting' Discovery Might Improve Cancer Treatment

March 30, 1999

CHAPEL HILL - University of North Carolina at Chapel Hill scientists have discovered they can shrink -- and in many cases eliminate - human tumors grown in laboratory animals by inhibiting a natural mechanism that prevents tumor cells from dying.

Although not yet tried directly in humans, scientists believe their technique could one day significantly improve survival among patients with many kinds of cancer. They are planning the first human tests, which should begin later this year.

The mechanism they've studied for more than three years involves NF-kappa B, a protein that attaches to DNA inside the nucleus of cells and turns genes on and off like a switch. Doctors use chemotherapy or radiation to kill cancer cells, but the UNC-CH researchers reported two and a half years ago that NF-kappa B kicks in and soon enables many cultured tumor cells to escape death. After developing resistance to the therapy, the cancer cells continue reproducing and show no ill effects from the treatment.

In the latest experiments, the scientists used a novel cancer gene therapy strategy to block NF-kappa B in mice with a natural inhibitor protein known as I-kappa B. Human tumors growing in the mice then became susceptible to chemotherapy and in some cases disappeared altogether following treatment.

A report on the discovery appears in the April issue of Nature Medicine, a scientific journal. Authors - all affiliated with the UNC Lineberger Comprehensive Cancer Center - are Dr. Cun-Yu Wang, a former graduate student and now clinical instructor in endodontics; Dr. James C. Cusack, assistant professor of surgery; laboratory technician Rong Liu; and Dr. Albert S. Baldwin Jr., associate professor of biology.

"Our results are dramatic, and we believe they are going to be extraordinarily important for therapy of different kinds of cancer," said Baldwin, associate director of the Lineberger Center. "Although not everything that works in animals also works in humans, many times they do work. Because we think this is a mechanism that is important generally, and we now know how to counteract it, we are very optimistic."

In the past, he said, no one has understood why many tumors don't respond to chemotherapy and radiation. NF-kappa B appears to be a front-line defense protecting both healthy cells and cancer cells from chemical attack.

In the new experiments, researchers concentrated on human colorectal and fibrosarcoma tumors. They grew the tumors in mice and then treated them with a modified form of the inhibitor I-kappa B carried by a virus that could enter tumor cells. Treatment with a commonly used chemotherapy compound known as CPT-11 was "eminently more successful," Baldwin said, when coupled with I-kappa B than when used by itself.

Cusack, a surgical oncologist specializing in gene therapy, agreed that results so far were "very exciting." He and colleagues are now devising tumor models for other forms of cancer and expect to win U.S. Food and Drug Administration approval for a variety of clinical trials based on the new findings.

"This forms the basis for developing a novel treatment strategy that is being explored further in preclinical studies and should be available to patients within the year," Cusack said. "These findings provide new insight into why many cancer cells frequently don't die when exposed to chemotherapy. The approach demonstrates a successful means of how we might overcome cancer cells' defense mechanisms to make treatment more effective."

He called the work a good example of the potential benefits of basic research that seeks to explain fundamental biology without preconceived notions and immediate applications.

Support for the studies came from the National Cancer Institute, the American Cancer Society, the UNC Lineberger Comprehensive Cancer Center and the Leukemia Society of America.
Note: Baldwin can be reached at 919-966-3652 or 966-3884, Cusack at 966-8007 or 216-3650.

University of North Carolina at Chapel Hill

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 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