Nav: Home

Antibody is effective against radiation-induced pulmonary fibrosis

March 31, 2017

Radiation therapy is part of the treatment regimen for about two thirds of cancer patients today. Radiotherapy is well tolerated in most cases, but it can also lead to damage in healthy tissues that are also irradiated. One debilitating side effect is radiation-induced fibrosis. Fibrosis is a process of scarring by which healthy tissue is replaced by less elastic connective tissue, which leads to hardening and functional impairments.

This process particularly affects the delicate tissues of the lungs when lung cancer is treated by radiation therapy. Fibrosis impairs gas exchange and thus causes shortness of breath in patients.

"We know that a whole number of growth factors and inflammation-promoting chemical messengers play a role in the development of fibrosis," said Peter Huber of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ). "But until now, agents targeting these molecules have not been effective enough to prevent pulmonary fibrosis or to improve its symptoms significantly. Much less was it possible to reverse fibrosis once it had developed. Therefore, we are urgently searching for targets that we can use to interrupt, slow down or even reverse this dreadful process."

In experiments with mice, Huber and his colleagues have now tested an antibody that blocks the connective tissue growth factor (CTGF), which is thought to be a key messenger in the transformation of connective tissue in the lungs. The researchers treated mice with the antibody for a period of eight weeks, starting at various time points before and after radiation treatment.

All therapy regimens protected up to 80 percent of the animals from fibrosis. When treatment was started 16 weeks after radiotherapy, the antibody reversed the fibrotic transformation. The density of the pulmonary tissue decreased by more than 50 percent, and pulmonary function and oxygen supply improved. After treatment had ended, the animals still maintained a stable health status and they survived considerably longer compared to untreated fellow animals.

When treatment with the antibody was started 20 days after radiotherapy, seventy percent of the mice survived a radiation dose that would otherwise have been lethal.

The antibody that the Heidelberg researchers used recognizes CTGF of mice as well as its human version. Based on the data obtained in the present work, it is already being studied in clinical trials for use against other types of fibrotic disease.

"The process of fibrotic tissue transformation following radiation therapy is very similar in mice and in men," said Sebastian Bickelhaupt, who is the study's first author. "This suggests that our results are also relevant for humans affected by fibrosis."

Irradiation of a tumor may cause fibrosis not only in the lungs but also in many other organs and may lead to considerable impairments in patients. This happens rather frequently in breast cancer, cancers of the head and neck and esophageal cancer as well as in gynecological cancers.

"The protection from fibrosis that we have been able to achieve using the antibody against CTGF in mice was impressive," Huber said. "We therefore think that it is promising to test the antibody also in humans who have to undergo radiotherapy. Additionally, patients with other types of fibrotic disease that are not related to radiation might also benefit from a blockade of CTGF. And maybe even the chances of curing the cancer will improve: If we reduce radiation-induced side effects, we can increase the radiation dose in the tumor."
-end-
Sebastian Bickelhaupt, Christian Erbel, Carmen Timke, Ute Wirkner, Monika Dadrich, Paul Flechsig, Alexandra Tietz, Johanna Pföhler, Wolfgang Gross, Peter Peschke, Line Hoeltgen, Hugo A. Katus, Hermann-Josef Gröne, Nils H. Nicolay, Rainer Saffrich, Jürgen Debus, Mark D. Sternlicht, Todd W. Seeley, Kenneth E. Lipson, Peter E. Huber: Effects of CTGF Blockade on Attenuation and Reversal of Radiation-Induced Pulmonary Fibrosis. Journal of the National Cancer Institute 2017, DOI 10.1093/jnci/djw339

German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)

Related Cancer Articles:

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.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
Health indicators for newborns of breast cancer survivors may vary by cancer type
In a study published in the International Journal of Cancer, researchers from the UNC Lineberger Comprehensive Cancer Center analyzed health indicators for children born to young breast cancer survivors in North Carolina.
Few women with history of breast cancer and ovarian cancer take a recommended genetic test
More than 80 percent of women living with a history of breast or ovarian cancer at high-risk of having a gene mutation have never taken the test that can detect it.
Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
More Cancer News and Cancer Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

In & Out Of Love
We think of love as a mysterious, unknowable force. Something that happens to us. But what if we could control it? This hour, TED speakers on whether we can decide to fall in — and out of — love. Guests include writer Mandy Len Catron, biological anthropologist Helen Fisher, musician Dessa, One Love CEO Katie Hood, and psychologist Guy Winch.
Now Playing: Science for the People

#543 Give a Nerd a Gift
Yup, you guessed it... it's Science for the People's annual holiday episode that helps you figure out what sciency books and gifts to get that special nerd on your list. Or maybe you're looking to build up your reading list for the holiday break and a geeky Christmas sweater to wear to an upcoming party. Returning are pop-science power-readers John Dupuis and Joanne Manaster to dish on the best science books they read this past year. And Rachelle Saunders and Bethany Brookshire squee in delight over some truly delightful science-themed non-book objects for those whose bookshelves are already full. Since...
Now Playing: Radiolab

An Announcement from Radiolab