Lung cancer differs in many aspects when it comes to smokers or non-smoker patients. The disease also responds differently to treatment in a person who has never smoked because of certain genetic changes, according to new research from Asia. These findings were published in the medical journal Cell today.
The findings from this new study can lead to better and new treatment options for non-smokers with lung cancer that target the newly identified genetic changes.
Resource in this issue of Cell: Proteogenomics of Non-smoking Lung Cancer in East Asia Delineates Molecular Signatures of Pathogenesis and Progression – https://t.co/oGcNWjOeQV
— Cell (@CellCellPress) July 9, 2020
This is the most comprehensive study of lung cancer in non-smokers ever conducted and was funded by Cancer Research UK and various institutions of Taiwan including the Ministry of Science and Technology.
Lung cancer is a serious disease. Nearly 20 percent of all cases of lung cancer occur in people who have never smoked or used tobacco in their life. If, lung cancer in non-smokers is considered a separate disease, it is one of the top 10 fatal cancers in United States.
In United Kingdom, 10 to 15 percent of all lung cancers occur in nonsmokers. This incidence is even higher in people in East Asia, especially women.
Lung cancer is caused by mutations and changes in the lining of the lung and why it happens in non-smokers has been an area of interest for scientists since many decades. In a similar effort to understand how lung cancer proceeds in Non-smokers while on treatment, scientists from Taiwan devised this large-scale study.
They studied a population which had high rates of cancer among non-smokers and found out that there were certain genetic changes associated with the condition, which were varying based on age or sex of a person.
In the study they saw that many non-smokers with lung cancer had signs of DNA damage from environmental carcinogens. Among them many young women in particular had distinctive genetic changes which can cause the cancer to evolve aggressively.
The study conducted by scientists in Taiwan in collaboration with UK Institute of Cancer Research, analyzed tumor samples from 103 lung cancer patients, of which mostly were nonsmokers.
They looked at a whole range of genetic changes, gene activation, protein activity and cellular ‘switches’ in lung cancer that happens in non-smokers during lung cancer, to find out how these factors influence the lung cancer treatment.
The Genetic Component
The first significant finding of the study was the fact that among tumor samples from early stage tumors in nonsmokers and late stage tumors in smokers, there were eerie biological similarities.
When they observed difference in genetic changes between men and women, they found that tumors in women often had fault in the lung cancer gene EGFR, whereas in men the most common faults were in the KRAS and APC genes. These differences can mean men and women will respond differently to different targeted drugs used for lung cancer treatment.
The study also found out that there was a special pattern of genetic changes involving the APOBEC gene family in nearly 3/4 of the tumor samples of women under the age 60 and in all women without faults in the EGFR gene.
APOBEC proteins are significant in cancer research because they have an important role in the immune system function. These proteins can also be over-taken by certain cancers, which can cause and speed up drug resistance to treatment.
It also means that patients can be screened for different types of treatment. As, patients without EGFR faults tend to do better on immunotherapy, women can be tested for the presence of APOBEC. This could help separate women who are more likely to respond to immunotherapy.
Another significant achievement of the team was to identify 65 proteins that were overactive in lung tumors and that matched with existing candidate drugs.
Another protein called MMP11, was also linked to poorer survival and was identified as biomarker that can be used for early detection of lung cancer.
The researchers plan to replicate their study in other parts of the world, to better understand how lung cancer evolves in non-smokers and to come up with new insights for treatment of the disease.
“Lung cancer is the biggest cancer killer in the UK, and much of what we know about the disease comes from studies in smokers. I’m hopeful that the new insights gleaned in this new study will really step up precision medicine in lung cancer for non-smokers, so they can be offered smarter, kinder treatment options.” said the Chief Executive of The Institute of Cancer Research, London, Professor Paul Workman, in a press release by the institute.