Small-cell lung cancer
Small-cell lung cancer (SCLC) is a significant type of lung cancer, accounting for around 15% of all cases. Unlike non-small-cell lung cancer (NSCLC), SCLC originates from neuroendocrine cells in the lungs. The primary risk factor for SCLC is smoking, responsible for 80-90% of lung cancer cases. Other risk factors include exposure to various toxic substances such as radon, asbestos, and certain metals, alongside genetic predispositions.
Early-stage SCLC may not present symptoms, but common signs include persistent cough, chest pain, unexplained weight loss, and difficulty breathing. Unfortunately, SCLC is often diagnosed after metastasis, meaning it has spread to other organs. Screening methods like spiral computed tomography (CT) have improved early detection rates, especially in high-risk individuals, compared to traditional methods like chest X-rays.
Treatment typically involves chemotherapy, primarily with platinum-based drugs, as surgical options are limited due to the advanced stage at which SCLC is often diagnosed. Prevention strategies emphasize the importance of avoiding smoking, with a significant reduction in risk occurring after quitting, although it never fully returns to baseline levels. Recent advancements in research and therapies could improve outcomes for SCLC patients in the future.
Small-cell lung cancer
ALSO KNOWN AS: Oat cell carcinoma; small-cell anaplastic carcinoma; undifferentiated small-cell carcinoma; intermediate cell type; and mixed small-cell/large-cell carcinoma.
DEFINITION Small-cell lung cancer (SCLC) is one of the two major types of lung cancer, the other being non-small-cell lung cancer (NSCLC). SCLC originates from nerve cells or hormone-producing cells in the lungs, whereas NSCLC originates from epithelial cells that make up the lining of the lungs.
Risk Factors
Smoking is the greatest risk factor for SCLC, with an estimated 80 to 90 percent of lung cancers caused by smoking. Other risk factors are exposure to radon, asbestos, beryllium, cadmium, silica, vinyl chloride, nickel- or chromium-containing compounds, coal products, mustard gas, chloromethyl esters, diesel exhaust, radiation to the chest, arsenic, air pollution, radioactive substances like uranium, and genetic factors.
Etiology and Genetics
The National Cancer Institute estimates that more than 221,097 new lung cancer cases and 125,070 deaths will occur in 2019, with SCLC accounting for about 15 percent of these. According to the same source, in 2021, 610,816 people in the United States were living with lung and bronchus cancer. Cancer in general is considered to be a genetic disease because cancer is associated with genetic changes in somatic cells that lead to uncontrolled cell growth. Lung cancer is not caused by a single gene. The human genome is made up of pairs of chromosomes. When tissue from the lungs of smokers is genetically analyzed, several areas of the DNA that makes up chromosomes and contain the genes are found to be damaged, duplicated, or missing. However, not all smokers with genetic damage in their lung tissue have lung cancer, suggesting that multiple sites of DNA damage must accumulate before lung cancer develops. Not every SCLC case has the same set of mutated genes present, but damage to specific regions on chromosomes 1, 3, 4, 5, 8, 9, 10, 11, 13, 15, 16, 17, 18, and 20 occurs frequently in SCLCs. In SCLC and other cancers, one of the most commonly mutated genes is called p53, a gene that usually causes damaged cells to undergo programmed cell death, known as apoptosis. When the p53 gene is mutated, the damaged cells do not die and can go on to become malignant cells.
While 85 percent of all lung cancers occur in former or current smokers, fewer than 20 percent of long-term smokers develop lung cancer, suggesting that genetic factors make some people more susceptible to lung cancer. In 2009, researchers identified two sites of genetic variation on chromosome 15 that people can inherit from their parents that are associated with an increased risk of lung cancer in smokers and former smokers. These genetic variations, called single nucleotide polymorphisms (SNPs), are places in the human genome that vary by a single DNA nucleotide. People who have one or two copies of either of these SNPs and who have ever smoked have increased risks of 28 percent to 81 percent of developing lung cancer. The two SNPs identified are near five genes on chromosome 15. Interestingly, three of these five genes encode proteins that serve as docking sites for nicotine, the addictive agent in tobacco. These findings suggest that nicotine, in addition to several known carcinogens present in tobacco smoke, may be involved in lung cancer development. Another of the genes near the SNPs encodes a component of the proteasome, an important organelle in cells that degrades other proteins. The function of the fifth gene is unknown.
Symptoms
In early-stage SCLC, patients often do not have symptoms. Symptoms of lung cancer include a cough that does not go away; chest pain that often gets worse with deep breathing, coughing, or laughing; hoarseness; unexplained weight loss or lack of appetite; bloody or rust-colored spit or phlegm (also called sputum); shortness of breath; recurrent infections like bronchitis and pneumonia; and new onset of wheezing. Small-cell lung cancer commonly spreads or metastasizes to other organs. Symptoms of cancer that has spread include bone pain; weakness or numbness in the limbs; headache, dizziness, or seizure; jaundice; and lumps near the surface of the body such as lymph nodes in the neck. Those who experience these symptoms should see a physician right away.
Screening and Diagnosis
Chest X-rays and checking sputum under a microscope to look for cancer cells was studied as a screening tool for lung cancer for several years. Unfortunately, this kind of screening is not very effective, with very few lung cancers found early enough to improve a person’s chances for a cure. Because this kind of screening is not very effective, it is not done routinely, even in smokers who are at high risk. However, a newer screening method, spiral computed tomography (CT) scanning, was tested in the National Lung Screening Trial from 2002 to 2010 and found more effective than chest X-rays at detecting cancer, and since 2013, medical authorities have recommended this form of screening for high-risk individuals. According to the National Cancer Institute in 2019, patients between fifty-five and seventy-four with a history of heavy smoking were 20 percent less likely to die from lung cancer if they underwent spiral computed tomography.
Treatment and Therapy
Small-cell lung cancer has usually spread or metastasized to other organs before it is diagnosed; therefore, it is usually not treated with surgery. Patients with advanced-stage disease are usually treated with platinum-based chemotherapy (cisplatin or carboplatin), which may be combined with the drugs etoposide or camptothecin-11. Patients whose tumors respond very well to chemotherapy may also be offered radiation therapy. According to the journal JAMA Oncology in 2024, because of recent test results and pharmaceutical approvals, the prognosis of patients with SCLC would likely be more promising in the future. Experts believed that these test results and drug approvals would lead to new, effective therapies.
Prevention and Outcomes
The most important prevention for SCLC is to not smoke, or to quit smoking. After quitting smoking, it takes about ten years to reduce the risk of lung cancer in former smokers, but the risk never drops to the level of those who never smoked.
Bibliography
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