Cancer of the lungs is driven primarily by polluted air from power houses and vehicles, as well as tobacco smoking. One way to classify the different types of lung cancer is based on the type of mutations that fuel the disease. For example, our ERC-supported project focuses on a type of lung cancer that is driven by a group of DNA defects collectively called EGFR mutations. Unlike the lung cancer of tobacco smokers, the class of EGFR-mutations is likely driven by tiny particles found in diesel exhaust and in other air pollutants. Fortunately, nearly 20 years ago some highly effective and relatively safe drugs were developed that prolonged the life expectancy of the respective patients. However, it was later found that almost all patients treated with the effective drugs, denoted EGFR inhibitors (EGFRi), become resistant to the drug. This necessitated development of new drugs. Similar to the first-generation drugs, the new drugs also achieved high efficacy and high safety. Unfortunately, however, patients treated with the new generation drugs also evolved resistance, and like in the first cycle, this was due primarily to the emergence of new mutations.
Along with the development of yet new drugs, a major mission currently undertaken by the pharmaceutical sector and the academic sector, including our ERC-supported team, concentrates on the mechanisms that propel the emergence of new mutations in patients undergoing treatment with EGFR inhibitors. Apparently, several biochemical mechanisms underlie the rapid generation of mutations in patients with lung cancer (approximately one year). Several years ago, we discovered that one mechanism undergoes activation when cancer cells are on the verge of dying due to the treatment with the first- or second-generation drugs. The mechanism, called SOS, is the major focus of our studies. Presumably, resolving the intricacies of the SOS process might identify ways to prevent emergence of new mutations. In other words, it is assumed that deep understanding of the SOS process will allow development of new drugs, or drug combinations, that are able to overcome or significantly delay the timing of the emergence of the new mutations.
