Quick Guide to Non-Small Cell Lung Cancer with ALK Positive Mutation
Lung cancer – Uncontrolled growth of abnormal cells in one or both lungs. It is the leading cause of death in men and women in the United States. Over 200,000 cases of lung cancer are diagnosed every year. Smoking is the leading cause of lung cancer, however, about 60% of those diagnosed with lung cancer have never smoked or are former smokers.
Three main types of lung cancer:
Non-small cell lung cancer (About 80%-85% of lung cancers)
Adenocarcinoma (roughly 40% of lung cancers) – Forms in the mucous secreting glands inside of organs like the lungs, colon, pancreas, and breasts.In the lungs it begins in the cells that line the alveoli (small grapelike structures in the lung that allow us to pass oxygen to the blood vessels)
Epidermal growth factor receptor (EGFR) – Present in roughly 15% of people with NSCLC in the U.S.
KRAS gene mutation – Present in roughly 30% of people with non-small cell lung cancer
Anaplastic lymphoma kinase (ALK) –Present in 3%-5% of people diagnosed with NSCLC (est. 10,000 people diagnosed with NSCLC w/ ALK mutation in 2017)
Squamous cell carcinoma
Large cell carcinoma
Small cell lung cancer (About 10%-15% of lung cancers, Forms in the actual tissues of the lungs, most commonly smokers develop SCLC)
Lung carcinoid tumor (About 5% of lung cancers, AKA lung neuroendocrine tumors, develop slowly and rarely spread
Taylor was diagnosed with Non-small cell lung adenocarcinoma with a positive ALK mutation
-Genes are the parts of chromosomes in our DNA that code for things such as our eye color and hair color. They are also the blueprint that codes for proteins that run the processes that keep our bodies running smoothly—or cause cells to divide and grow.
-ALK (anaplastic lymphoma kinase) is a gene that tells your body how to make proteins that help cells talk to each other. In lung cancer with an ALK rearrangement, part of this gene is broken and attached to another gene. The new fused gene turns code and creates an abnormal protein called tyrosine kinase. The tyrosine kinase (mutated gene) is what drives the growth of the cancer. (This re-arrangement can also be found in neuroblastoma and anaplastic large cell lymphoma)
-ALK mutation was discovered in 2007 - Often younger patients — usually 55 and under — who have never smoked are most likely to be diagnosed as being ALK+. In a recent study, it was found that patients younger than 40 years of age tested positive for EML4-ALK fusion gene almost 50% of the time. (In contrast to the 3%-5% of people of all ages with lung cancer).
IMPORTANT NOTE: The EML4-ALK fusion gene isn’t a hereditary mutation found in some people with breast cancer (and some other cancers.) People who have a lung cancer positive for the EML4-ALK fusion gene weren’t born with cells that had this mutation and didn’t inherit a tendency to have this mutation from their parents. Instead, this is an acquired mutation that develops in some cancer cells as a part of cancer development.
-Why do these genes all of a sudden mutate, you ask? No one knows this…yet. They do know, however, instances of young, non-smokers developing NSCLC is on the rise.
Symptoms: A cough that will not go away, chest pain, persistent hoarseness, weight loss, coughing up blood, shortness of breath, fatigue and weakness, wheezing, and pneumonia
Diagnosis: Generally symptoms give a provider reason to obtain a chest x-ray which would reveal an abnormal mass or finding. From there a CT scan may be performed. A sample must be obtained from tissue or fluid from in or around the lung. (Bronchoscopy, endobronchial ultrasound, thoracentesis, Thoracoscopy, or fine needle aspiration). If positive, tumors are sent for genomic testing to look for genetic changes.
Treatment: Although ALK rearrangements were just discovered, numerous treatments have already been approved by the FDA which has drastically increased survival time.
-Tyrosine kinase inhibitors – block the signals given by the ALK-EML4 fusion protein and inhibit the growth of cancer. Alectinib (alencensa), Xalkori (crizotinib), Zykadia (ceritinib), Lobrena (loratinib)
-Alectinib was recently named the first line of treatment for NSCLC w/ ALK
-These drugs are not a cure for lung cancer, but something that keeps the cancer “in check”
-Over 50% of patients respond well to inhibitors initially (Closer to 70% with the approval of alencensa). Unfortunately resistance almost always develops anywhere from months to years later. Tumors change over time and develop new mutations. Sometimes a medication that targets another treatable mutation (such as EGFR) may work even though a tumor was not initially positive for an EGFR mutation.
-Other treatment options include: Clinical trials, chemo, radiation, immunotherapy.
Eldridge, L. (2019, January 2). All About ALK Positive Lung Cancer. Retrieved from https://www.verywellhealth.com/alk-positive-lung-cancer-definition-and-treatment-2248944
Lung Cancer. (n.d.). Retrieved from https://www.cancer.org/cancer/lung-cancer.html
Sullivan, I., & Planchard, D. (2015). ALK inhibitors in non-small cell lung cancer: The latest evidence and developments. Therapeutic Advances in Medical Oncology, 8(1), 32-47. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4699265/.
What Is Non-Small Cell Lung Cancer? (n.d.). Retrieved from https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/what-is-non-small-cell-lung-cancer.html