The Effectiveness of Treatments in Non-Small Cell Lung Cancer with affected ALK Genes

Author(s): Kenneth Axelbank

Mentor(s): Janna Mattson, Honors College

Abstract

The topic of research intends to explore the treatments available for Non-Small Cell Lung Cancer patients that have had their ALK gene altered. There are several treatments that have tested to work with ALK gene mutations and researching the similarities of these treatments could allow for a breakthrough in treatments that could work across various gene mutations. ALK stands for Anaplastic Lymphoma Kinase which represents the ALK gene. The study will also investigate the work of inhibitors through the treatment process and the inhibition of cancer cells. The EGFR inhibitors block the activity of a specific protein with the name of epidermal growth factor receptor. With new research being made, there can be an increased option for treatments for patients. MET alterations are another aspect related to lung cancer that needs to be analyzed. MET gene amplification is a way to resist first and third generation EGFR inhibitors in lung cancer treatment. Understanding MET alterations that are repetitive can help understand the tests for ALK-positive traits in lung cancer. This topic of research consists of properly understanding the ALK gene alterations in lung cancer and the inhibitors and amplifications that are effective in treatments. 

Video Transcript

Hello, my name is Kenneth Axelbank, and this presentation will primarily focus on “What treatments prove most effective with non-small cell lung cancer patients with affected ALK genes?” This topic may have some complex concepts to comprehend, so some key terms are laid out. First off, the ALK gene is known as the anaplastic lymphoma kinase gene. This gene provides instructions for constructing a protein called the ALK receptor tyrosine kinase which is a family of proteins called receptor tyrosine kinases (RTKs). RTKs will not be discussed throughout the presentation as such they are not included in the key terms. The genes that are mentioned in the key terms are the genes discussed in some peer review articles. These articles analyze genetic material which has a direct effect on lung cancer related mutations. There are two types of lung cancer one being non-small cell lung cancer and the other being small cell lung cancer. Non-small cell lung cancer is abbreviated as NSCLC and small cell lung cancer as SCLC. NSCLCs are more deadly than SCLCs which is why there is an emphasis on research for NSCLC. the met pronto oncogene is a growth factor receptor and stands for the met gene. Crizotinib and Ceritinib are two treatments that are effective in NSCLC for ALK mutated genes. KRAS, EGFR and ROS1 genes are other NSCLC related genes that can be affected. Fish assay testing is an available detection test for ALK rearrangements where it is possible to detect whether cancer cells have mutated with the ALK gene this study primarily focuses on the investigation of inhibitors and their effectiveness in the process of treatment. This research is significant in creating new treatments for future ALK and alterations due to the adaptation of cancer cells growing and current treatments becoming less effective as stated in the key terms there are two types of lung cancer.  In most types of cancer there are different stages, in lung cancer there are four stages and the higher the stage the mortality rate and the cancer cell dispersion will be significantly increased. The future of gene sequences can adjust depending on the mutation and cancer cells which could adapt to treatments.  The first article focuses on fish assay testing for the ALK gene while looking at other genes through their respective detection tests. There were approximately 73 patients observed during this study. Out of the 73 patients, four of these cases could not be analyzed due to insufficient tumor material. Three other cases had assay failure which resulted in inaccurate fish assay test results. Out of the 42 ALK negative cases that occurred, seven of these cases presented possibilities for EGFR mutations which were mutations from another gene. This article ended by pointing to further research being made in high-risk genetic environmental factors. The second article focuses on Ceritinib which is an available treatment for NSCLC and ALK mutations. The significance of this article relays on the analyzation of key points in Ceritinib such as its design development and place in treatment. The methods used in this experiment were situ hybridization which specifically locates tumor cells and strands of DNA/RNA. This article gives some background on Ceritinib treatment and discusses a comparison to other treatments. Overall, Ceritinib may be effective currently but it does have a high chance of becoming less effective as time goes on just as every other treatment available. The further action will be researching the sequences of ALK affected genes and predicting the next sequences that ALK mutations would have. For the third study, the focus is was on the implications of fish positive patterns in NSCLC patients. The methods consisted of fish assay testing and this was a recently published article. There was a flaw found in patients receiving false positive results, so this research found a way to identify the possibility of an inaccurate result. This was done by analyzing patterns in these patients. 40 patients were tested with the goal of establishing a connection between NSCLC patients and fish positive patterns. Lastly met alterations in ALK positive NSCLC were focused on the realization that this research made was that FISH assay testing works for met alterations in some cases. The levels of MET amplification were analyzed in the study. This would lead to possibilities in combinations of ALK/MET treatments that were meant for ALK positive NSCLC patients. To conclude, there has been considerable research on ALK mutations in NSCLC, however there is always more to learn and more research to advance our knowledge of lung cancer and its impact on people. It was found that Ceritinib is more effective than Crizotinib which would be the assumption as Crizotinib was exposed to cancer cells before Ceritinib was. Also analyzing ALK genes is important to learn more and synthesize newer treatments. More research is needed, but there should be an emphasis on research centered around a comparative analysis on detection tests and treatments. Overall, the ALK gene is one gene that is affected by cancer cells but this also means that there is possibility for other treatments to work on this gene and for a treatment specific to the ALK gene to work on other genes. This hypothesis could lead to eliminating cancer cells and other genes using treatments that could be effective for more than one gene planned follow-on research consists of analyzing at least two different specific gene treatments and how their attributes can be combined to create a more effective treatment for more than one gene. The works cited includes citations for four research articles and the pictures used for the first and last slide.

One reply on “The Effectiveness of Treatments in Non-Small Cell Lung Cancer with affected ALK Genes”

Your mention of specific genes is really interesting. It’s clear that you went in-depth in your literature review to grasp a full understanding of the topic and research needs. Great presentation!

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