Changes in the genome separate cells from the ordered cell structure, proliferate unchecked and displace healthy tissues. The other mutations, in turn, ensure that the cancer cells escape the immune defense. Some of these genetic and epigenetic regulatory features that make cancer cells particularly dangerous on the one hand are now known, but they can also be targets for new active ingredients on the other hand.
Attack points for new active ingredients
The pathway from healthy body cells to cancer cells causes mutations: Through changes in the genetic makeup, cells break away from the organized cell structure, multiplying unimpeded and displacing healthy tissues. The other mutations, in turn, ensure that the cancer cells escape the immune defense. Some of these genetic and epigenetic regulatory features that make cancer cells particularly dangerous on the one hand are now known, but they can also be targets for new active ingredients on the other hand.
At the 61st Congress of the German Society of Pneumology and Respiratory Medicine H. V. (DGP), which will be held online from June 2 to 6, 2021. The topic will also be featured in the online press conference accompanying the conference on Thursday, June 3, 2021.
With more than 50,000 new cases annually, lung cancer (bronchial cancer) is the most common type of cancer in Germany. At the same time, it is also one of the most dangerous diseases: about 35,000 people die every year from cancer, which often spread before it was discovered. But not all lung cancer is the same. Professor Dr. says. Average. Gernot Rode, Head of Respiratory Medicine / Allergy at University Hospital Frankfurt and Chair of this year’s DGP Conference. These properties have been deciphered more precisely in recent years, paving the way for personalized precision medicine.
The starting point for driver mutations: inhibiting signaling pathways, slowing tumor growth
One area of intense research is so-called driver booms. Through this, the cancer cells separate their growth from the external influencing factors. “Normally, cell growth and division are stimulated by growth factors that bind to specific receptors on the cell surface,” explains Rudi. This sets up a chain of multi-stage signals moving inside the cell, in which a number of enzymes are involved, including so-called tyrosine kinases. Mutations are found in every fourth of non-small cell lung cancer (NSCLC) that keep the signaling pathway permanently active, even without growth factors. “With the help of active ingredients that inhibit tyrosine kinases, tumor growth can be slowed in patients with this type of lung cancer,” says Rudd.
This increased their average survival time from 9.6 to 31.5 months. Another active ingredient is currently being developed, which uses the K-RAS enzyme to manipulate downstream linkage in the signal chain. “Until now there is no treatment option for patients with K-RAS mutations because tyrosine kinase inhibitors do not work here,” said Rudd. The new K-RAS inhibitor has already proven effective in Phase 2 clinical studies and could slow the course of the disease in about 37 percent of the patients examined.
Immune checkpoints in focus: re-enabling immune defense
Another goal of individual cancer treatment is what are called immune checkpoints. “Many lung cancer cells increasingly develop special surface molecules that prevent immune cells from attacking them,” explains Rudi. With the help of new antibody-based active ingredients, this inhibition has become increasingly possible – cancer cells can then be recognized as dangerous by the immune system and killed. Particularly combined with chemotherapy, this greatly increases the survival time of patients. “The discovery of immune checkpoints and driver mutations, as well as specially designed active ingredients, has revolutionized lung cancer treatment in recent years,” summed up the DGP conference chair.
At the Congressional press conference for the 61st DGP Conference, which will be held online on June 3, 2021, Rohde will also talk about the genetic changes that underlie cystic fibrosis. More than 1,000 different mutations have now been identified here, some of which can actually be addressed in terms of personalized precision medicine with specially developed active ingredients.
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