Small cell lung cancer (SCLC) is considered an aggressive form of lung cancer. It is mainly characterized by the rapid and uncontrollable growth of some abnormal cells within the lungs. It results in tumor formation leading to the metastasis of cancerous cells that is spread to the different body parts. Small cell lung cancer (SCLC) has been estimated to cause 15% of lung cancer being diagnosed in other regions of the globe. Its primary characteristic is its higher proliferation rate and significant sensitivity to the chemotherapy treatment. Smoking is the leading risk factor that causes lung cancer adhering to 85% of the cases. The other risk factors include second-hand smoke, asbestos, radon, and other environmental factors. Smoking is mainly concerned with all major types of lung cancer. The strongest association is the small cell lung cancer and squamous cell lung cancer. Cigarette smoke consists of many organic and inorganic carcinogens involving polycyclic aromatic hydrocarbons (PAHs), aromatic amines, N-nitrosamines, benzene, vinyl chloride, arsenic, and chromium, among many others.
Smoking has affected most of the population of developing countries while causing lung cancer and specifically small cell lung cancer. The significant incidence of small cell lung cancer has tended to lower since past decades, representing the decrease in smoking prevalence, changes to cigarettes, and reduced occupational hazards. Therefore, the primary risk factor for SCLC is tobacco use, as most affected individuals are habitual to smoking or possess a history of smoking. Symptoms mainly vary as per the individuals, and very rare common symptoms have been diagnosed in the initial phase of the disease. Mainly small cell lung cancer is divided into two major stages, the limited stage disease that has the chances of getting cured among 20%-25% of the individuals and extensive stage disease that represents difficulty in treating the disease. The affected individuals are given chemotherapy treatment and radiation therapy. Surgery is recommended for a small group of individuals during the early stage of cancer. Different clinical trials have progressed with targeted therapies to treat small cell lung cancer.
Small cell lung cancer is characterized as neuroendocrine carcinoma due to the features of nerve cells and endocrine (hormone-secreting) cells within the tumour cells. Endocrine tissue is the specialized tissue containing hormone-secreting cells resulting in multiple functions within the body. The initial occurrence of small cell lung cancer starts by altering the healthy cells within the lungs that later show uncontrollable growth, forming a lesion or a nodule. The SCLC begins in the nerve cells or hormone-producing cells within the lungs. The term small cell is associated with the size and shape of the cancer cells, as seen under a microscope. As the tumour grows, cancer cells are shredded, which can be later carried away in blood and float away in the fluid, known as lymph, surrounding the lung tissue. Lymph flows through tubes called lymphatic vessels that drain into the lymph nodes. Lymph nodes are the small, bean-shaped organs that fight the infection. These are located within the lungs, a central region of the chest and other body parts. The lymph commonly flows outwards towards the chest region, describing the initial metastasis of SCLC. The small cell lung cancers are very quick to show metastasis, and several individuals diagnosed with SCLC are already observed with metastasis to other body parts.
SCLC is mainly divided into two subtypes: oat cell carcinoma and combined-SCLC. Combined SCLC is the SCLC with non-small cell components involving squamous cells or adenocarcinoma. SCLC carcinogenesis is integrated through different pathways that disrupt standard DNA repair mechanisms. The most common mutations in SCLC affect the loss of the RB1 tumor suppressor gene and TP53(17p13) modifications that aim to decrease the tumor cells’ apoptotic mechanism. Almost all the types of SCLC tumors show a deletion section associated with the short arm of chromosome 3p containing the tumor suppressor gene FHIT 1. Neuroendocrine features commonly represent the SCLC. Depending upon the WHO classification, the neuroendocrine tumors of the lung involve either SCLC, large cell carcinoma with neuroendocrine features, carcinoids, or combined SCLC. SCLC is the high-grade neuroendocrine tumor showing faster doubling time and KI-67 of 50–100% 2. SCLC is composed of small blue cells with a small amount of cytoplasm, necrosis and crush artefact.
Approximately 5% of the small cell lung cancer patients have been asymptomatic at presentation. Some of the most common symptoms occurring in the advanced stage of SCLC involve breathing shortness, cough, bone pain, fatigue, weight loss, and neurologic dysfunction. Most patients with this disease possess a short duration of symptoms, usually only 8-12 weeks before presentation. The clinical manifestations of SCLC can result from local tumor growth, intrathoracic spread, distant spread, and paraneoplastic syndromes. A two-thirds majority of patients have distant metastatic disease at initial diagnosis. Most of the common metastasis sites for SCLC include the contralateral lung, the brain, liver, adrenal glands, and bone. The concentration of circulating tumor cells (CTCs) in SCLC is considered the highest of any solid tumor 3.
As small cell lung cancer is characterized by rapid growth and early dissemination, immediate treatment is critical. This treatment approach is based on the types of stage of SCLC the patient is diagnosed with. The clinical aspects of minor cell lung cancer treatment involve surgery and adjuvant platinum-based chemotherapy. The patients diagnosed with early-stage or locally advanced disease are given concurrent radiation and platinum-based chemotherapy. The SCLC patients with metastatic disease are given systemic chemotherapy with or without immunotherapy. SCLC shows effective response towards cytotoxic therapies among almost 25% of patients with early-stage SCLC, achieving long-term control of small cell lung cancer with concurrent chemoradiotherapy (CRT) 2,4. It presents response rates consistently over 60%, even in patients with metastatic disease.
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