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 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 growth factor (CTGF), which is thought to be a key messenger in the transformation of 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 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 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 will improve: If we reduce -induced side effects, we can increase the in the tumor."

Explore further: New paste prevents scarring caused by radiation therapy for cancer

More information: Sebastian Bickelhaupt et al, Effects of CTGF Blockade on Attenuation and Reversal of Radiation-Induced Pulmonary Fibrosis, JNCI: Journal of the National Cancer Institute (2017). DOI: 10.1093/jnci/djw339

Related Stories

New paste prevents scarring caused by radiation therapy for cancer

January 4, 2016
An antiscarring paste when applied to the skin of mice halts fibrosis caused by the radiation used in cancer therapy. That is according to a study led by researchers at Laura and Isaac Perlmutter Cancer Center to be published ...

Researchers discover link between aging, devastating lung disease

February 23, 2017
A Mayo Clinic study has shown evidence linking the biology of aging with idiopathic pulmonary fibrosis, a disease that impairs lung function and causes shortness of breath, fatigue, declining quality of life, and, ultimately, ...

World first trial of shark inspired drug

January 31, 2017
La Trobe University scientists are preparing to run a world-first clinical trial of a new drug inspired by shark antibodies. The drug, AD-114, is a human protein that is based on the shape of an antibody of a Wobbegong shark.

Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer

February 16, 2017
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.

Discovery offers hope for new Crohn's disease treatment

September 2, 2016
Scientists at the University of British Columbia have made a discovery that could potentially lead to treatments for a debilitating complication of Crohn's disease.

Recommended for you

What does hair loss have to teach us about cancer metastasis?

December 15, 2017
Understanding how cancer cells are able to metastasize—migrate from the primary tumor to distant sites in the body—and developing therapies to inhibit this process are the focus of many laboratories around the country. ...

Cancer immunotherapy may work better in patients with specific genes

December 15, 2017
Cancer cells arise when DNA is mutated, and these cells should be recognized as "foreign" by the immune system. However, cancer cells have found ways to evade detection by the immune system.

Scientists pinpoint gene to blame for poorer survival rate in early-onset breast cancer patients

December 15, 2017
A new study led by scientists at the University of Southampton has found that inherited variation in a particular gene may be to blame for the lower survival rate of patients diagnosed with early-onset breast cancer.

Scientists unlock structure of mTOR, a key cancer cell signaling protein

December 14, 2017
Researchers in the Sloan Kettering Institute have solved the structure of an important signaling molecule in cancer cells. They used a new technology called cryo-EM to visualize the structure in three dimensions. The detailed ...

'Bet hedging' explains the efficacy of many combination cancer therapies

December 14, 2017
The efficacy of many FDA-approved cancer drug combinations is not due to synergistic interactions between drugs, but rather to a form of "bet hedging," according to a new study published by Harvard Medical School researchers ...

Liquid biopsy results differed substantially between two providers

December 14, 2017
Two Johns Hopkins prostate cancer researchers found significant disparities when they submitted identical patient samples to two different commercial liquid biopsy providers. Liquid biopsy is a new and noninvasive alternative ...

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.