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Lung Cancer Growth Reduced To Half By Max Planck Researchers

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Lung Cancer Growth Reduced To Half By Max Planck Researchers

Researchers from the Max Planck Institute for Heart and Lung Research in Bad Nauheim and Justus Liebig University Giessen, have made further progress in the treatment of lung cancer. Scientists were able to reduce tumor growth in mice by 50% by blocking PDE 4(phosphodiesterase). Angiogenesis is one of the most studied targets of anticancer treatment. For tumor cells to grow and form a tumor mass, they need a blood supply provided by blood vessels that circulate oxygen and nutrients. Growth of new blood vessels (angiogenesis) is triggered by the hypoxia, ie oxygen shortage. Also, growth of blood vessels is achieved by different signaling  messengers (cAMP, cGMP).

Lung Tumor

Lung Tumor

Bevacizumab, for example, an angiogenesis inhibitor, is one of the drugs that are used to treat metastatic cancer. Bevacizumab is a monoclonal antibody which inhibits vascular endothelial growth factor A (VEGF-A). Basically, it was approved by the FDA for the treatment of metastatic colon cancer. Then it  was accepted for treatment of other cancers such as lung cancer, renal cancer and glioblastoma multiforme.

PDE is an enzyme that degrades certain compounds in signaling messengers, like cAMP and cGMP. There are several types of phosphodiesterases, some of which generate cAMP (PDE 4, 7, 8), others that generate cGMP (PDE 5, 6, 9). Some can hydrolyze both cAMP and cGMP (PDE 1, 2, 3, 10, 11). Because it is involved in growth of blood vessels that nourish tumors, researchers thought to inhibit PDE 4 to prevent tumor growth. Thus, they blocked PDE 4 in 10 cell lines that  are responsible for most lung cancers. By inhibiting PDE4, PDE4 is activated for a longer time and this will determine an increased  amount of cAMP in cells. cAMP in turn phosphorylate proteins (protein kinase A, protein kinase C) and triggers a whole cascade of cellular events.

After the experiment, the researchers found that cell division in cells treated with inhibitor of PDE 4 was significantly reduced. Then researchers implanted human tumor tissue in mice that were then treated with PDE 4 inhibitor. The result was positive in the sense that tumor dimensions were reduced by approximately 50%. The researchers noted that PDE4 inhibition has led not only to reduced blood vessel growth but also reduced tumor cell division.

Werner Seeger, Director of the MPI and Medical Director of the JLU Giessen University Hospital, said:  “We were able to show that PDE4 plays an important regulation function in cell division in lung tumours and in the development of blood vessels in cancer”. He also added that this discovery is the starting point for possible future treatments for lung cancer among  chemotherapy and radiotherapy.