What is Lung Adenocarcinoma?
Non-Small Cell Lung Cancers (NSCLC) are the most common type of lung cancer and are usually less aggressive than Small Cell Lung Cancer [1].There are three subtypes in NSCLC patients, including Squamous Cell, Large Cell and Lung Adenocarcinoma (LADC), all illustrated bellow.
Risk factors for LADC include specific genetic mutations or tissue damage from old age, Radon and most importantly inhaled substances. This may include vaping, tobacco or marijuana smoke or air pollutants [2].
However, treatment and prognosis for this disease is restricted by our understanding of the cellular mechanisms that underly human biology. Geneticists study the association between disease associated characteristics (phenotypes) and the contents of our genome (genotype). Although this type of research is important and is the focus of this website, avoiding inhaled substances, such as cigarette smoke are equally important. Physiological effects of quitting cigarettes or other tobacco products can be drastic after a short time.
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Cellular mechanisms of LADC
LADC starts by uncontrollable cell growth that can ultimately spread to other parts of the body. This disease starts in the outer part of the lung, usually in epithelial tissue [3]. Symptoms of LADC include persistent cough, shortness of breath, chest pain, unexplained weight loss and sometimes death, according to the American Cancer Society [4]. This organization specializes in clinical research on the underlying physiological and genetic causes of LADC as well as drug therapy and is a good resource for supplementary information.
Non-specific treatments of this disease aren't enough to inhibit cell proliferation in clinical cases (Arora, et al., 2017, pg. 2). Specifically, LADC is Resistant to conventional radio- and chemotherapies which create a challenge for effective clinical treatment. More specific targeting at the specific genetic pathways related to aggressive tumor cell growth are necessary, which is has been accomplished through cell cycle inhibitors, such as Tyrosine Kinase Inhibitors.
Non-specific treatments of this disease aren't enough to inhibit cell proliferation in clinical cases (Arora, et al., 2017, pg. 2). Specifically, LADC is Resistant to conventional radio- and chemotherapies which create a challenge for effective clinical treatment. More specific targeting at the specific genetic pathways related to aggressive tumor cell growth are necessary, which is has been accomplished through cell cycle inhibitors, such as Tyrosine Kinase Inhibitors.
Mis-regulation of cell migration, proliferation and apoptosis ultimately disrupts regular lung function [5]. As shown on the left, cancer cells can be converted or differentiate themselves. These changes are important for understanding how normal epithelial cells can gain different function. In cancer, these functions include movement and uncontrollable cell growth (proliferation), which is also illustrated in the image.
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Mesenchymal stem cells seemed to have an important role in epithelial initiated tumor growth. The Epidermal Growth Factor Receptor (EGFR) may play a part in cellular mechanisms that control cancer cell behavior and accumulation [3]. Genetics research mainly focuses on the gene and its affects on normal cellular processes. More specifically, understanding the role EGFR has in cell growth, proliferation and migration is important to LADC.
Studying these effects can be seen in other mammals. For example, the Velvet mutation is a naturally occurring change in the EGFR gene that causes abnormal epithelia growth in the eyelid [6]:
Studying these effects can be seen in other mammals. For example, the Velvet mutation is a naturally occurring change in the EGFR gene that causes abnormal epithelia growth in the eyelid [6]:
Epithelial cell growth is linked to cancer and as described above, the EGFR gene. One main contributor is known as the Epithelial Mesenchymal Transition (EMT) [7]. Furthermore, Mesenchymal transitions can contribute to cancer through cell proliferation and migration, as illustrated in one of the previous figures.
What information is on this website?
In the accompanying pages, the EGFR gene, will be characterized in the context of epithelial cell transitions, migration and proliferation that all play a part in LADC. Hopefully, compiling information relevant to these cellular processes can help people to be informed about the genetics aspects of this disease.
References:
1.) Rhonan Arora, Venkat Krishnan, et al. (2017). Selective Targeting of the L858R Mutation(EGFR) in Non-Small Cell Lung Cancer: A Mechanism for Advancing Targeted Chemotherapy [Pubmed Article]. Retreived from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5447734/pdf/fonc-07-00104.pdf
2.) Non-Small-Cell Lung Cancer [Web MD. Article]. Retrieved from: https://www.webmd.com/lung-cancer/non-small-cell-lung-cancer#1
3.) Rooney C., Sethi T., The Epithelial Cell and Lung Cancer: The Link between Chronic Obstructive Pulmonary Disease and Lung Cancer (2011). Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5447734/pdf/fonc-07-00104.pdf
4.) American Cancer Society, Signs and Symptoms of Lung Cancer (2019). Retrieved from: https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/signs-symptoms.html
5.) Nele Van Der Steen, et al., (2018). Resistance to epidermal growth factor receptor inhibition in non-small cell lung cancer [Pubmed Article]. Retrieved from https://cdrjournal.com/article/view/2823
6.) Tabeta, Hoebe, et al., Velvet, a Dominant Egfr Mutation That Causes Wavy Hair and Defective Eyelid Development in Mice (2004). Retrieved from: https://www.genetics.org/content/166/1/331
7.) New insights into the mechanisms of epithelial–mesenchymal transition and implications for cancer Anushka Dongre & Robert A. Weinberg (2019). Retrieved from: https://www.nature.com/articles/s41580-018-0080-4