Lung cancer is the cancer with the highest global incidence and its mortality in the UAE is the third highest in absolute numbers, considering patients up to 74 years of age. In addition, 4.25 million cases are estimated in 2045, almost double the number observed in 2022 worldwide. Thus, understanding the causes that lead to the disease has revolutionized its treatment and allowed the development of therapies focused on genetic alterations present in the tumor.
In absolute numbers, the incidence of lung cancer was the highest among cancers in 2022, considering both sexes and global data. Next come breast and colorectal cancers, three of which account for more than 25% of cases.
SOURCE: IARC.FR
Lung cancer includes 2 subtypes: non-small cell lung cancer (NSCLC), the most frequent, and small cell lung cancer. In any case, the differences between the subtypes and cell populations in the two tumor classes point to the need to identify mutations through panels or exome sequencing. Next, some mutations will be addressed. Their identification allows more specific treatment strategies to be outlined, and their presence is of great importance for the mode of progression in lung cancers.
In UAE, the absolute numbers of mortality in lung cancer are the third highest cancer among people of both sexes and up to 74 years of age, reaching 25 thousand victims in 2022.
SOURCE: IARC.FR
EGFR gene mutations are among the most common genetic changes in NSCLC, particularly in adenocarcinoma. These mutations lead to the activation of the EGFR tyrosine kinase, promoting uncontrolled cell proliferation. EGFR mutations are more prevalent in lung cancers of non-smokers and individuals of East Asian ancestry.
ALK gene rearrangements, such as EML4-ALK fusion, occur in a subset of NSCLC patients. These rearrangements produce an abnormal ALK protein that drives the growth of cancer cells. ALK-positive lung cancers tend to occur in younger, non-smoking patients.
The presence of oncogenic mutations in these two genes makes tumors more sensitive to therapies that involve tyrosine kinase inhibition. This inhibition resulted in the recommendation of tests for the evaluation of EGFR and ALK in patients with NSCLC lung cancer for the application of this inhibitory therapy, given its success in several cases. Examples of inhibitors are the drugs erlotinib, gefitinib, osimertinib for EGFR and crizotinib, ceritinib, and alectinib for ALK.
Other already defined mutations bring the challenge of identifying effective inhibitors to hinder cancer progression. This is the case of mutations in the KRAS gene, found in approximately 25% of lung adenocarcinomas. Such mutations lead to the activation of the RAS/MAPK pathway, contributing to the survival and proliferation of cancer cells. KRAS mutations are often associated with a history of smoking. A recent breakthrough is the inhibitor sotorasib, which targets a specific mutation (G12C) in KRAS.
An increase of nearly two million cases of lung, bronchial and tracheal cancers is expected between 2022 and 2045 worldwide in people up to the age of 85.
SOURCE: IARC.FR
Rearrangement mutations in the ROS1 gene occur in a low percentage (1-2%) of NSCLC but generate a fusion protein that guides tumor growth and are more common in non-smokers. Fortunately, an inhibitor cited above for ALK, crizotinib, has efficacy against tumors containing these rearrangements. Another more specific inhibitor for ROS1 is entrectinib.
The well-known V600E variant in the BRAF gene and others in this same gene are seen in some cases and are responsible for the activation of a MAPK/ERK signaling pathway, which promotes cell proliferation. It is common for this mutation to occur together with others, which can make it difficult to decide on treatment choices. For the V600E mutation, inhibitors such as dabrafenib in combination with other inhibitors (such as trametinib for MEK) have shown success.
Conclusion
Lung cancer is a diverse disease with some defined subtypes. Some recurrent mutations point the way to targeted treatments, and the use of panels or broader sequencing allows for their identification. Learn about mutations in ALK, EGFR and 26 other gene markers of importance through one of our Genetic Panel for Liquid Biopsies – contact us about the Panel for Liquid Biopsies for Lung Cancer.
To learn more about treatment options and actionable and accurate recommendations for mutations identified in lung or other tumor cancers, learn about our computational protocol and oncology report, GTX-Onco.
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