Lung cancer , also known as lung carcinoma , is a malignant lung tumor characterized by uncontrolled cell growth in lung tissue. This growth can spread beyond the lungs through metastatic processes to nearby tissues or other parts of the body. Most of the lung cancer, known as primary lung cancer, is a carcinoma. The two main types are small cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC). The most common symptoms are cough (including coughing up blood), weight loss, shortness of breath, and chest pain.
Most (85%) of cases of lung cancer are due to long-term tobacco smoking. Approximately 10-15% of cases occur in people who never smoked. These cases are often caused by a combination of genetic factors and exposure to radon gas, asbestos, passive smokers, or other forms of air pollution. Lung cancer can be seen on chest radiography and computed tomography (CT) scans. Diagnosis is confirmed by biopsy usually performed by bronchoscopy or CT-guidance.
Avoiding risk factors, including smoking and air pollution, is a major preventive method. Treatment and long-term outcomes depend on the type of cancer, stage (spread rate), and overall health of a person. Most cases can not be cured. Common treatments include surgery, chemotherapy, and radiotherapy. NSCLC is sometimes treated with surgery, whereas SCLC usually responds better to chemotherapy and radiotherapy.
Around the world in 2012, lung cancer occurs in 1.8 million people and resulting in 1.6 million deaths. This makes it the most common cause of cancer-related death in men and second most common in women after breast cancer. The most common age at diagnosis is 70 years. Overall, 17.4% of people in the United States who were diagnosed with lung cancer survived five years after diagnosis, while the average outcome was worse in developing countries.
Video Lung cancer
Signs and symptoms
Signs and symptoms that may indicate lung cancer include:
- Respiratory symptoms: cough, coughing up blood, wheezing, or shortness of breath
- Systemic symptoms: weight loss, weakness, fever, or fingers on toenails
- Symptoms due to suppression of cancer mass in adjacent structures: chest pain, bone pain, superior vena cava obstruction, or difficulty swallowing
If the cancer grows in the airways, it can block airflow, causing breathing difficulties. Obstruction may cause accumulation of secretions behind blockage, and is susceptible to pneumonia.
Depending on the type of tumor, the paraneoplastic phenomenon - a symptom not due to the local presence of the cancer - may initially draw attention to the disease. In lung cancer, this phenomenon may include hypercalcaemia, inappropriate antidiuretic hormone syndrome (SIADH, abnormally concentrated urine and diluted blood), ectopic ACTH production, or Lambert-Eaton myastenia syndrome (muscle weakness due to autoantibodies). Tumors at the top of the lungs, known as Pancoast tumors, can attack the local part of the sympathetic nervous system, leading to Horner's syndrome (dropping the small eyelids and pupils on the side), and damaging the brachial plexus.
Many symptoms of lung cancer (poor appetite, weight loss, fever, fatigue) are not specific. In many people, the cancer has spread beyond the original site when they have symptoms and seek medical attention. Symptoms suggesting metastatic disease include weight loss, bone pain and neurologic symptoms (headache, fainting, seizures, or limb weakness). Common sites of spread include the brain, bone, adrenal gland, opposite lung, liver, pericardium, and kidney. About 10% of people with lung cancer have no symptoms at diagnosis; This cancer is accidentally found on routine thoracic radiography.
Maps Lung cancer
Cause
Cancer develops after genetic damage to DNA and epigenetic changes. These changes affect normal cell function, including cell proliferation, programmed cell death (apoptosis), and DNA repair. As more damage accumulates, the risk of cancer will increase.
Smoking
Smoking tobacco is by far the major contributor to lung cancer. Cigarette smoke contains at least 73 known carcinogens, including benzo [ a ] pyrene, NNK, 1,3-butadiene, and radioactive isotopes of polonium-polonium-210. Around the world advanced, 90% of lung cancer deaths in men and 70% in women in 2000 were associated with smoking. Smoking accounts for about 85% of cases of lung cancer.
Passive smoking - inhaling smoke from someone else's cigarettes - is the cause of lung cancer in people who do not smoke. Passive smokers can be defined as someone who lives or works with a smoker. Studies from the US, Europe and the UK have consistently shown a significant increase in risk among those exposed to passive smoking. Those who stay with someone who smokes have an increased risk of 20-30% while those working in the environment with passive smokers have a 16-19% increase in risk. Investigation of sidestream smoke shows that it is more dangerous than direct smoke. Passive smoking generates about 3,400 lung cancer-related deaths each year in the US.
Marijuan smoke contains many of the same carcinogens as tobacco smoke. However, the effects of smoking marijuana on lung cancer risk are unclear. Overview 2013 found no increased risk from light to moderate use. A review of 2014 found that smoking marijuana doubles the risk of lung cancer.
Radon gas
Radon is a colorless and odorless gas produced by the breakdown of radioactive radium, which in turn is the uranium decay product, found in the Earth's crust. The radiation decay product ionizes the genetic material, causing mutations that sometimes become cancerous. Radon is the second most common cause of lung cancer in the US, causing about 21,000 deaths each year. Risk increases 8-16% for every 100 Bq/m³ peningkatan increase in radon concentration. The rate of radon gas varies according to the locality and the composition of the underlying soil and rocks. About one in 15 homes in the US has radon levels above the recommended guidelines of 4 picocuries per liter (pCi/l) (148 Bq/mÃ,³).
Asbestos
Asbestos can cause various lung diseases such as lung cancer. Smoking tobacco and asbestos both have a synergistic effect on the development of lung cancer. In smokers working with asbestos, the risk of lung cancer increased 45-fold compared with the general population. Asbestos can also cause pleural cancer, called mesothelioma - which is actually different from lung cancer).
Air pollution
External air pollutants, especially chemicals removed from burning fossil fuels, increase the risk of lung cancer. Fine particles (PM 2.5 ) and sulfate aerosols, which may be released in traffic exhaust fumes, are associated with a slightly increased risk. For nitrogen dioxide, a gradual increase of 10 parts per billion increases the risk of lung cancer by 14%. Outdoor air pollution is thought to cause 1-2% lung cancer.
Temporary evidence supports the increased risk of lung cancer from indoor air pollution in relation to wood burning, charcoal, dirt, or crop residue for cooking and heating. Women exposed to indoor coal smoke have twice the risk, and many of the byproducts of biomass combustion are known or suspected carcinogens. This risk affects about 2.4 billion people worldwide, and is believed to lead to 1.5% of lung cancer deaths.
Genetics
About 8% of lung cancers are caused by inherited factors. In the family of people diagnosed with lung cancer, the risk is multiplied, probably due to a combination of genes. Polymorphisms on chromosomes 5, 6, and 15 are known to affect the risk of lung cancer.
Other causes
Many other substances, occupations, and environmental exposures have been linked to lung cancer. The International Agency for Research on Cancer (IARC) states that there is some "sufficient evidence" to suggest that the following are carcinogenic in the lungs:
- Some metals (aluminum production, cadmium and cadmium compounds, chromium compounds (VI), beryllium and beryllium, iron and steel, nickel compounds, arsenic and inorganic arsenic compounds, and underground hematite mining)
- Some products from burning (incomplete combustion, coal (indoor emissions from household coal burning), coal gasification, coal pitch, coke production, soot, and diesel engine disposal)
- Ionizing radiation (X-radiation, gamma radiation, and plutonium)
- Some toxic gases (methyl ether (technical grade), and Bis- (chloromethyl) ether, sulfur mustard, MOPP (mixture of mustard-procarbazine vincristine-prednisone-nitrogen) and smoke from painting)
- Production of crystal silica rubber and dust
- There is a small increase in the risk of lung cancer in people affected by systemic sclerosis.
Pathogenesis
Similar to many other cancers, lung cancer is initiated by oncogen activation or inactivation of tumor suppressor genes. Carcinogens cause mutations in genes that trigger cancer progression.
Mutations in proto-oncogenes cause about 10-30% of pulmonary adenocarcinoma. Nearly 4% of small non-cell lung carcinomas involve the fusion gene of the EML4-ALK tyrosine kinase.
Epigenetic changes such as changes in DNA methylation, histone tail modification, or microRNA regulation may lead to inactivation of tumor suppressor genes.
Epidermal growth factor receptor (EGFR) regulates cell proliferation, apoptosis, angiogenesis, and tumor invasion. EGFR mutations and amplification are common in non-small cell lung carcinomas, and they provide the basis for treatment with EGFR-inhibitors. Her2/neu is affected less frequently. Other genes that often mutate or amplify include c-MET , NKX2-1 , LKB1 , PIK3CA , and < i> BRAF .
Original cell line is not fully understood. This mechanism may involve abnormal activation of stem cells. In the proximal channel, stem cells that express keratin 5 are more likely to be affected, usually causing squamous cell lung carcinoma. In the middle airways, involved stem cells include club cells and neuroepithelial cells that express the protein cell secretion of the club. Small cell lung carcinomas may originate from these cells or neuroendocrine cells, and may express CD44.
Lung cancer metastasis requires transition from epithelial cell type to mesenchymal. This can occur through activation of signaling pathways such as Akt/GSK3Beta, MEK-ERK, Fas, and Par6.
Diagnosis
Chest X-ray is one of the first investigative steps if a person reports symptoms that may indicate lung cancer. This may reveal a clear mass, dilation of mediastinum (suggestive of spreading to lymph nodes there), atelectasis (collapse), consolidation (pneumonia), or pleural effusion. CT imaging is usually used to provide more information about the type and extent of disease. Bronchoscopy or CT-guided biopsy is often used for tumor samples for histopathology.
Lung cancer often appears as a solitary pulmonary nodule on thoracic radiography. However, the differential diagnosis is widespread. Many other diseases can also provide this appearance, including metastatic cancer, hamartoma, and infectious granulomas such as tuberculosis, histoplasmosis, and coccidioidomycosis. Lung cancer may also be an incidental finding, as solitary pulmonary nodules on chest radiographs or CT scans are performed for unrelated reasons. The definitive diagnosis of lung cancer is based on suspicious tissue histological examination in the context of clinical and radiological features.
The clinical practice guidelines recommend frequencies for the monitoring of pulmonary nodules. CT imaging should not be used longer or more frequently than indicated, since extended surveillance exposes people to radiation enhancement.
Classification
Lung cancer is classified by histologic type. This classification is important to determine management and predict the outcome of the disease. Lung cancer is a carcinoma - a malignancy arising from epithelial cells. Pulmonary carcinoma is categorized by the size and appearance of malignant cells seen by histopathologists under a microscope. For therapeutic purposes, two broad classes are distinguished: non-small cell lung carcinoma and small cell lung carcinoma.
Non-small cell lung carcinoma
The three major subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.
Nearly 40% of lung cancers are adenocarcinomas, which usually originate from peripheral lung tissue. Although most cases of adenocarcinoma are associated with smoking, adenocarcinoma is also the most common form of lung cancer among people who smoke less than 100 cigarettes in their lives ("never smoked") and former smokers with a simple smoking history. Subtypes of adenocarcinoma, bronchioloalveolar carcinoma, are more common in women who never smoked, and may have better long-term resilience.
Squamous cell carcinoma causes about 30% of lung cancer. They usually occur close to large airways. Hollow cavities and associated cell death are commonly found in the center of the tumor. Nearly 9% of lung cancers are large cell carcinomas. This is so named because of its massive cancer cells, with excess cytoplasm, large nuclei, and prominent nucleoli.
Small-cell lung carcinoma
In small cell lung carcinomas (SCLC), cells contain dense neurosecretic granules (vesicles containing neuroendocrine hormones), which give these tumors an association of endocrine/paraneoplastic syndrome. Most cases occur in larger airways (primary and secondary bronchi). Sixty to seventy percent have extensive disease (which can not be targeted in the field of single radiation therapy) during presentation.
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Four major histologic subtypes are recognized, although some cancers may contain different combinations of subtypes, such as adenosquamous carcinoma. Rare subtypes include carcinoid tumors, carcinoma of the bronchial glands, and sarcomatoid carcinoma.
Metastasis
The lungs are a common place for the spread of tumors from other parts of the body. Secondary cancer is classified by the home site; for example, breast cancer that has spread to the lungs is called metastatic breast cancer . Metastasis often has a distinctive rounded image on chest x-rays.
Primary lung cancer also most often metastasizes to the brain, bone, liver, and adrenal glands. Immunostaining biopsy usually helps determine the original source. The presence of Napsin-A, TTF-1, CK7, and CK20 help confirm the subtype of lung carcinoma. SCLC derived from neuroendocrine cells can express CD56, nerve cell adhesion molecule, synaptophysin, or chromogranin.
Staging
Lung cancer staging is an assessment of the extent of cancer spread from the original source. This is one of the factors that affect both the prognosis and the potential treatment of lung cancer.
Evaluation of non-small-cell lung carcinoma (NSCLC) staging using TNM classification. It is based on the size of the t umor, the major n ode lymph node involvement, and the distant etastasis m .
Using TNM descriptor, the group was assigned, ranging from occult cancer, through stages 0, IA (one-A), IB, IIA, IIB, IIIA, IIIB, and IV (four). This stage group helps with treatment options and prognostic estimates.
Small-cell lung carcinomas (SCLC) have traditionally been classified as "limited stages" (limited to one-half of the chest and within the scope of a single tolerable radiotherapy field) or "broad stage" (wider disease). However, TNM classification and clustering are useful in estimating prognosis.
For both NSCLC and SCLC, two common types of staging evaluations are clinical staging and surgical staging. Clinical staging is performed before definitive surgery. This is based on the results of imaging studies (such as CT scans and PET scans) and biopsy results. Surgical staging is evaluated either during or after surgery. This is based on the combined results of surgical and clinical findings, including surgical sampling of the thoracic lymph node.
- Main feature staging diagram
Prevention
Prevention of smoking and smoking cessation is an effective way to prevent the development of lung cancer.
Smoking ban
While in most countries industrial and domestic carcinogens have been identified and banned, tobacco smoking is still widespread. Eliminating smoking habits is a major goal in the prevention of lung cancer, and quitting smoking is an important preventative tool in this process.
Policy interventions to reduce passive smoking in public places such as restaurants and workplaces have become more common in many Western countries. Bhutan has had a complete smoking ban since 2005 while India introduced a public smoking ban in October 2008. The World Health Organization has called on the government to institutionalize a total ban on tobacco advertising to prevent young people from smoking. They considered that the ban had reduced tobacco consumption by 16% where it was institutionalized.
Screening
Cancer screening uses medical tests to detect disease in large groups of people who have no symptoms. For individuals at high risk of developing lung cancer, computed tomography (CT) screening can detect cancer and give a person the option to respond in a life-prolonging way. This form of screening reduces the likelihood of death from lung cancer by an absolute 0.3% (relative 20%). High risk people are those aged 55-74 who smoke the same number of packs of cigarettes every day for 30 years including the time in the last 15 years.
CT screening is associated with a high false-positive test rate that can lead to unnecessary treatment. For every real positive scan there are about 19 false positive scans. Other concerns include radiation exposure and testing costs as well as follow-up. Research has not found two other tests available - sputum cytology or chest radiography (CXR) - to get any benefit.
The United States Agency for Prevention Task Force (USPSTF) recommends annual screening by using low-dose computed tomography in those with a 30-year total smoking history and aged between 55 and 80 years until someone has not smoked for more than one 15 years. Screening should not be done on those with other health problems that would make lung cancer treatment if no choice was found. The UK's National Health Service in 2014 re-examined evidence for screening.
Other prevention strategies
Long-term use of vitamin A supplements, vitamin C, vitamin D or vitamin E does not reduce the risk of lung cancer. Some studies show that people who eat a diet with a higher proportion of vegetables and fruits tend to have lower risks, but this may be due to assimilation - with lower risk actually due to a high fruit/vegetable diet association with less smoking. Some rigorous studies have not shown a clear relationship between diet and lung cancer risk, although a meta-analysis that takes into account smoking status may indicate the benefits of a healthy diet.
Management
Treatment for lung cancer depends on the type of cancer-specific cells, how far the spread, and status of one's performance. Common treatments include palliative care, surgery, chemotherapy, and radiation therapy. Targeted lung cancer therapy is increasingly important for advanced lung cancer.
Surgery
If investigations confirm NSCLC, this stage is assessed to determine whether the disease is localized and inoperable or if it has spread to a point where it can not be cured by surgery. CT scans and positron emission tomography are used for this determination. If there is suspected mediastinal lymph node involvement, the nodes may be sampled to aid the staging. Techniques used for this include transthoracic needle aspiration, transbronchial needle aspiration (with or without endobronchial ultrasound), endoscopic ultrasound with needle aspiration, mediastinoscopy, and thoracoscopy. Blood tests and lung function tests are used to assess whether a person is fit enough for surgery. If lung function tests reveal poor respiratory reserves, surgery may not be possible.
In most cases of early stage NSCLC, removal of the lobe (lobectomy) is the preferred surgical treatment. In people unsuited to full lobectomy, smaller sublobar excisions (wedge resection) may be performed. However, wedge resection has a higher recurrence risk than lobectomy. Brachytherapy radioactive iodine on the edges of the slice excision may reduce the risk of recurrence. Rarely, removal of the entire lung (pneumonectomy) is done. Video-assisted thoracoscopic surgery (VATS) and VATS lobectomy use a minimally invasive approach to lung cancer surgery. VATS lobectomy is as effective as conventional open lobectomy, with less postoperative disease.
In SCLC, chemotherapy and/or radiotherapy is usually used. But the role of operations in SCLC is being reconsidered. Surgery can improve results when added to chemotherapy and radiation in early SCLC.
Radiotherapy
Radiotherapy is often given along with chemotherapy, and can be used with curative intentions on people with NSCLC who are not eligible for surgery. This form of radiotherapy with high intensity is called radical radiotherapy. Completion of this technique is a continuous hyperfraction acceleration radiotherapy (CHART), in which high-dose radiotherapy is given in a short period of time. Postoperative piston radiotherapy generally should not be used after curative surgery for NSCLC. Some people with involvement of mediastinal lymph nerve may benefit from postoperative radiotherapy.
For the case of potentially curable SCLC, chest radiotherapy is often recommended in addition to chemotherapy.
If cancer growth blocks a short section of the bronchus, brachytherapy (local radiotherapy) can be given directly in the airway to open the way. Compared with external emission radiotherapy, brachytherapy allows for reduced maintenance time and reduced radiation exposure to health care staff. The evidence for brachytherapy, however, is less than that for external beam radiotherapy.
Prophylactic cranial irradiation (PCI) is a type of radiotherapy to the brain, used to reduce the risk of metastasis. PCI is most useful in SCLC. In limited-stage disease, PCI improves three-year survival from 15% to 20%; in the widespread disease, the survival of one year increased from 13% to 27%.
Recent improvements in targeting and imaging have led to the development of stereotactic radiation in the treatment of early-stage lung cancer. In the form of this radiotherapy, high doses are administered through a number of sessions using stereotactic targeting techniques. Its use is mainly in patients who are not surgical candidates due to medical comorbidities.
For patients with NSCLC and SCLC, smaller doses of radiation to the chest can be used for symptom control (palliative radiotherapy).
Chemotherapy
Chemotherapy regimens depend on the type of tumor. Small cell lung carcinoma (SCLC), even relatively early stage disease, is treated primarily with chemotherapy and radiation. In SCLC, cisplatin and etoposide are most commonly used. Combinations with carboplatin, gemcitabine, paclitaxel, vinorelbine, topotecan, and irinotecan are also used. In non-small cell pulmonary carcinoma (NSCLC), chemotherapy improves survival and is used as first-line treatment, provided that the person is well enough for treatment. Usually, two drugs are used, one of which is often platinum-based (either cisplatin or carboplatin). Other commonly used drugs are gemcitabine, paclitaxel, docetaxel, pemetrexed, etoposide or vinorelbine. Platinum-based drugs and combinations that include platinum therapy may cause a higher risk of serious adverse events in people over the age of 70.
Adjuvant chemotherapy refers to the use of chemotherapy after curative surgery to improve outcomes. In NSCLC, samples were taken from adjacent lymph nodes during surgery to help staging. If stage II or III disease is confirmed, adjuvant chemotherapy (including or excluding postoperative radiotherapy) increases survival by 4% over five years. The combination of vinorelbine and cisplatin is more effective than older regimens. Adjuvant chemotherapy for people with stage IB cancer is controversial, as clinical trials have not clearly demonstrated survival benefits. Preoperatively operating chemotherapy in NSCLC can improve yield.
Chemotherapy can be combined with palliative care in the treatment of NSCLC. In advanced cases, proper chemotherapy improves the average survival of supportive care, and improves quality of life. With adequate physical fitness retain chemotherapy during palliative lung cancer offers 1.5 to 3 months of survival extension, symptom relief, and improved quality of life, with better results seen with modern agents. The NSCLC Meta-Analyses Collaborative Group recommends that if the recipient wants and tolerates treatment, chemotherapy should be considered in advanced NSCLC.
Targeted therapies
Some drugs that target molecular pathways in lung cancer are available, especially for the treatment of advanced disease. Erlotinib, gefitinib and afatinib inhibit tyrosine kinase at epidermal growth factor receptors. Denosumab is a monoclonal antibody directed against the activator of the kappa-B ligand nuclear factor receptor. This may be useful in the treatment of bone metastases.
Bronchoscopy
Some treatments may be given via bronchoscopy for the management of airway obstruction or bleeding. If the airway is hampered by cancerous growth, options include rigid bronchoscopy, balloon bronchoplasty, stenting, and microdebridement. Laser photosection involves sending a laser beam inside the airway through the bronchoscope to remove the blocking tumor.
Palliative care
Palliative care when added to ordinary cancer treatments benefits people even when they are still receiving chemotherapy. This approach allows additional discussion of treatment options and provides an opportunity to arrive at well-considered decisions. Palliative care may avoid unhelpful but expensive treatments not only at the end of life, but also throughout the course of the disease. For individuals who have more advanced disease, home care treatments may also be appropriate.
Prognosis
Of all people with lung cancer in the US, 16.8% survived for at least five years after diagnosis. In England and Wales, between 2010 and 2011, the overall five-year survival for lung cancer is estimated at 9.5%. Results are generally worse in developing countries. Staging often progresses at the time of diagnosis. At presentation, 30-40% of cases of NSCLC are stage IV, and 60% SCLC is stage IV. Survival for lung cancer decreased as the diagnosis became more advanced: English data showed that about 70% of patients survived at least one year when diagnosed at the earliest stage, but this dropped to just 14% for those diagnosed with the most advanced. disease.
Prognosis factors in NSCLC include presence of pulmonary symptoms, large tumor size (& gt; 3 cm), nonsquamous (histological) cell type, extent of staging and metastasis to multiple lymph nodes, and vascular invasion. For people with an inoperable disease, worse outcomes in those with poor performance status and weight loss of more than 10%. Prognostic factors in small cell lung cancer include performance status, sex, stage of disease, and central nervous system or liver involvement at diagnosis.
For NSCLC, the best prognosis is achieved by complete surgical resection of stage IA disease, with a survival of five years to 70%. People with widespread SCLC had an average five-year survival rate of less than 1%. The mean survival time for end-stage disease is 20 months, with a five-year survival rate of 20%.
According to data provided by the National Cancer Institute, the average age at the diagnosis of lung cancer in the United States is 70 years, and the average age at death is 72 years. In the US, people with medical insurance are more likely to have better results.
Epidemiology
Worldwide, lung cancer is the most common cancer among men in terms of incidence and death, and among women has the third highest incidence, and second only to breast cancer in mortality. In 2012, there are 1.82 million new cases worldwide, and 1.56 million deaths from lung cancer, representing 19.4% of all cancer deaths. The highest rates in North America, Europe and East Asia, with more than a third of new cases in China that year. Levels in Africa and South Asia are much lower.
The segments of the population most likely to develop lung cancer are those over 50 who have a history of smoking. Unlike the death rate in men - which began to decline more than 20 years ago, the lung cancer mortality rate for women has increased over the last few decades, and has recently begun to stabilize. In the US, lifetime risk for developing lung cancer is 8% in men and 6% in women.
For every 3-4 million cigarettes smoked, one lung cancer death can occur. The influence of "Great Tobacco" plays an important role in smoking. Younger nonsmokers who see tobacco advertising are more likely to smoke. The role of passive smoking is increasingly recognized as a risk factor for lung cancer, resulting in policy interventions to reduce unwanted exposure of non-smokers to someone else's cigarette smoke.
In the US, black men and black women have a higher incidence. The rate of lung cancer is currently lower in developing countries. As smoking increases in developing countries, tariffs are expected to increase in the next few years, particularly in China and India.
Also in the US, military veterans have rates of lung cancer 25-50% higher mainly due to higher smoking rates. During World War II and the Korean War, asbestos also played a role, and Agent Orange may have caused some problems during the Vietnam War.
Lung cancer is the third most common cancer in the UK (about 46,400 people diagnosed with disease in 2014), and it is the most common cause of cancer-related deaths (about 35,900 people died in 2014).
From the 1960s, the level of pulmonary adenocarcinoma began to increase in relation to other types of lung cancer, in part due to the introduction of cigarette strainers. The use of filters removes larger particles from tobacco smoke, thereby reducing deposition in larger airways. However, smokers should inhale more deeply to receive the same amount of nicotine, increasing the deposition of particles in the small airways where adenocarcinomas tend to appear. The incidence of pulmonary adenocarcinoma continues to increase.
History
Lung cancer is rare before the onset of cigarettes; it was not even recognized as a different disease until 1761. A different aspect of lung cancer was described further in 1810. Malignant lung tumors accounted for only 1% of all cancers seen at autopsy in 1878, but have increased to 10- 15% by the early 1900s. Case reports in medical literature amounted to only 374 worldwide in 1912, but an autopsy review showed the incidence of lung cancer had increased from 0.3% in 1852 to 5.66% in 1952. In Germany in 1929, physician Fritz Lickint recognize the relationship between smoking. and lung cancer, leading to an aggressive anti-smoking campaign. The British Doctors' Study, published in the 1950s, is the first strong epidemiological evidence of a link between lung cancer and smoking. As a result, in 1964, the General General of the United States recommended that smokers should stop smoking.
Relations with radon gas were first recognized among miners in the Ore Mountains near Schneeberg, Saxony. Silver has been mined there since 1470, and the mine is rich in uranium, with radium and the accompanying radon of gas. Miners developed a disproportionate amount of lung disease, eventually recognized as lung cancer in the 1870s. Despite this discovery, mining continued into the 1950s, due to the Soviet Union's demand for uranium. Radon was confirmed as a cause of lung cancer in the 1960s.
The first successful pneumonectomy for lung cancer was performed in 1933. Palliative radiotherapy has been used since the 1940s. Radical radiotherapy, originally used in 1950, is an attempt to use larger radiation doses in patients with relatively early-stage lung cancer, but who are otherwise unfit for surgery. In 1997, hyperfractionated accelerated radiotherapy was continuously viewed as an improvement over conventional radical radiotherapy. With small cell lung carcinoma, early attempts in the 1960s on surgical resection and radical radiotherapy were unsuccessful. In the 1970s, a successful chemotherapy regimen was developed.
Direction of research
The current research direction for the treatment of lung cancer includes immunotherapy, which encourages the immune system to attack tumor cells, epigenetics, and a combination of new chemotherapy and radiotherapy, both on their own and together. Many of these new treatments work through blockade of immune blocks, interfering with the ability of the cancer to evade the immune system.
Ipilimumab blocks signals through receptors in T cells known as CTLA-4 that suppress the immune system. It has been approved by the US Food and Drug Administration (FDA) for the treatment of melanoma and is undergoing clinical trials for non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC).
Other immunotherapy treatments interfere with the binding of programmed cell 1 (PD-1) protein death with PD-1 ligand ligand 1 (PD-L1), and have been approved as first-line treatment and subsequently for various subset of lung cancers.. Signaling through PD-1 inactivates T cells. Several cancer cells appear to exploit this by expressing PD-L1 to kill T cells that might recognize them as a threat. Monoclonal antibodies targeting PD-1 and PD-L1, such as pembrolizumab, nivolumab, atezolizumab, and durvalumab are currently in clinical trials for the treatment of lung cancer.
Epigenetics is the study of minor, usually inherited, molecular - or "mark" modifications - that bind DNA and alter the rate of gene expression. Targeting this tag with drugs can kill cancer cells. Early-stage studies in NSCLC using drugs aimed at epigenetic modification suggest that blocking more than one of these tags can kill cancer cells with fewer side effects. Studies have also shown that giving patients these drugs before standard treatment can improve their effectiveness. Clinical trials are underway to evaluate how well these drugs kill lung cancer cells in humans. Some drugs that target the epigenetic mechanism are under development. Histone deacetylase inhibitors in development include valproic acid, vorinostat, belinostat, panobinostat, entinostat, and romidepsin. DNA methyltransferase inhibitors in development include decitabine, azacytidine, and hydralazine.
The TRACERx project looks at how NSCLC develops and evolves, and how these tumors become resistant to treatment. The project will look at tumor samples from 850 NSCLC patients at various stages including diagnosis, after first treatment, post-treatment, and relapse. By studying the samples at different tumor development points, the researchers hope to identify the changes that promote tumor growth and resistance to treatment. The results of this project will help scientists and doctors gain a better understanding of NSCLC and potentially lead to the development of new treatments for this disease.
For cases of lung cancer that develop resistance to the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor, a new drug is under development. New EGFR inhibitors include afatinib and dacomitinib. The alternative signaling pathway, c-Met, can be inhibited by tivantinib and onartuzumab. New ALK inhibitors include crizotinib and ceritinib. If the MAPK/ERK pathway is involved, BRAF dabrafenib and MAPK/MEK inhibitor trametinib inhibitors may be useful.
Lung cancer stem cells are often resistant to conventional chemotherapy and radiotherapy. This can cause relapse after treatment. The new approach targets proteins or glycoprotein markers specific to stem cells. These markers include CD133, CD90, ALDH1A1, CD44 and ABCG2. Signaling paths like Hedgehog, Wnt, and Notch are often involved in stem cell updates. So treatments that target these pathways can help prevent a recurrence.
References
External links
- Lung cancer in Curlie (based on DMOZ)
Source of the article : Wikipedia
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