Breakthrough links COPD, emphysema and lungcancer

By Hudson Institute communications. Reviewed by Dr Mohamed Saad

Professor Brendan Jenkins and Dr Mohamed Saad from the Cancer and Immune Signalling Research Group at Hudson Institute
L–R: Dr Mohamed Saad and Professor Brendan Jenkins

Hudson Institute scientists have paved the way to potentially test new treatments for chronic obstructive pulmonary disease (COPD) and emphysema, following a discovery of the molecular drivers of these lung diseases.

The impact of COPD and emphysema

COPD is a leading cause of morbidity and mortality worldwide and a major risk factor for developing lung cancer. In Australia, approximately one in every 20 Australians aged 45 years and over suffers from COPD.

Key points

  • Key discovery: Hudson Institute scientists identified the enzyme ADAM17 as a central molecular driver of COPD and emphysema, linking these diseases to lung cancer.
  • Therapeutic potential: The discovery suggests that targeting ADAM17 with newly-developed inhibitors could offer effective treatments for COPD, emphysema, and potentially prevent lung cancer.
  • Research implications: This breakthrough paves the way for testing ADAM17 inhibitors in pre-clinical models and developing new therapeutic strategies.

Limitations to current treatment

The main goal of existing therapies for emphysema and COPD is to relieve symptoms, prevent complications and slow the progression of the disease, however, there is no known effective therapy to cure these diseases.

Key discovery: the role of ADAM17

Leading inflammation researchers Dr Mohamed Saad and Professor Brendan Jenkins discovered that an enzyme – ADAM17 – acts as a central molecular switch that leads to pulmonary emphysema.

Increased activation of ADAM17 was identified as a hallmark of COPD and emphysema in patients and in preclinical models, providing a possible driving force that fuels the development of lung cancer in COPD patients.

The protease ADAM17 acts as a ‘scissor’ to cut off particular inflammatory proteins on the cell membranes. These released proteins then activate inflammatory and carcinogenic processes that lead to COPD and cancer. “We propose that overactive ADAM17 may be the link between COPD and lung cancers,” Dr Saad said.

Potential for new treatments

The discovery paves the way for inhibitor drugs that target ADAM17 to block its activity, which have recently been developed, to potentially treat COPD and emphysema and to develop other innovative new treatments.

“Our research focuses on identifying new drug targets for the treatment of pulmonary emphysema, which is the major debilitating component of COPD,” said Prof Jenkins, who leads this research.

Future directions

This study means we could be able to test whether newly-developed ADAM17 inhibitors will effectively block emphysema and COPD in pre-clinical models, paving the way for these inhibitors to be considered in the future to treat patients,” he said.

Significance of the discovery

“This is the first time that ADAM17 inhibition has been shown to be a promising treatment strategy for COPD and emphysema,” Prof Jenkins said.

The research, published in the American Journal of Respiratory Cell and Molecular Biology, studied ADAM17 protein expression and activation in lung biopsies from emphysema patients, and in preclinical models of emphysema and acute exposure to cigarette smoke.

ADAM17 was found to be a ‘bone fide mechanistic link between the pathogenesis of COPD and lung cancer,’ the study said.

“Our study places the protease ADAM17 as a pivotal inducer of pulmonary emphysema and a central mechanistic link between cigarette smoke, COPD (emphysema) and lung cancer,” Dr Saad said.

He said further studies could pave the way to identifying innovative therapeutic avenues to treat these lung diseases.

COPD facts

  • COPD is a leading cause of morbidity and mortality worldwide and a major risk factor for developing lung cancer.
  • In Australia, approximately one in every 20 Australians aged 45 years and over suffers from COPD.
  • COPD is characterised by progressive and persistent airflow limitation, and comprises a diverse group of lung pathologies with disparate clinical presentations, mainly chronic bronchitis an emphysema.

Collaborators | Christian-Albrechts-University, Kiel, Germany, RMIT University, Victoria, Australia

This research was supported by | NHMRC, United States Department of Defense, Victorian Government Operational Infrastructure Support Program, Cancer Council Victoria (CCV)

Journal | American Journal of Respiratory Cell and Molecular Biology

Title | ADAM17 Deficiency Protects against Pulmonary Emphysema

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