Introduction
Research in lung cancer treatment can save lives and improve a patient’s quality of life. There are three main types of lung cancer: Non-small cell, small cell, and lung carcinoid cancer. Non-small cell lung cancer, such as Squamous cell carcinoma, adenocarcinoma, and large cell carcinoma make up about 85% of all lung cancers (Molina, Yang, Cassivi, Schild, & Adjei, 2008). Both environmental and genetic factors are significant in the cause of lung cancer. Chronic exposure to carcinogens, ionizing radiation, and viral infections can lead to alterations of the DNA in tissue lining the bronchial epithelium of the lungs. Furthermore, genetic abnormalities in tumor suppressor gene inactivation and over activity of growth generates oncogenes (Fong, 2003). Today, roughly only 15% of lung cancer patients survive more than 5 years after diagnosis (Lee, Loo, Traini, & Young, 2015). This shows that diagnosis and treatment could be drastically improved. Classical treatments include surgery, radiation therapy, chemotherapy, and often all three treatments can be used. Surgery is the primary treatment option for early stage lung cancers (Sadhukha, Wiedmann, & Panyam, 2013). More recently, nanomedicine is becoming more attractive in lung cancer treatment. Pulmonary drug delivery systems made of polymeric nanoparticles, liposomes, or micelles are designed to specifically target the lungs. Although nanotechnology has many benefits there are still challenges to overcome.
The economic impact of lung cancer in the western parts of the world is staggering and tends to have the largest economic burden when compared to other forms of cancer. In 2011 the estimated total healthcare costs for all forms of cancer was $88.7 billion ("Economic Impact of Cancer," n.d.). Lung cancer has been estimated to make up 20% of all cancer-related healthcare costs, which is estimated to be roughly $17.74 billion (Goodwin & Shepherd, 1998). In the European Union (EU), lung cancer was estimated to have the highest economic cost of any other type of cancer and was found to make up 15% of all cancer related costs at $21.4 billion (converted from 18.8 billion euros) (Luengo-Fernandez, Leal, Gray, & Sullivan, 2013). Lung cancer has been characterized as a high-cost illness, not only in its totality, but at a per-patient level as well ("Economic considerations in the care of lung cancer patients.: Current Opinion in Oncology," n.d.).
Lungs are a pair air-filled organs located on either side of the chest, also known as thorax. The trachea conducts air into the lungs through the bronchi (tubular tubes). The bronchi then divide into the bronchioles (smaller branches) ("Lungs (Human Anatomy): Picture, Function, Definition, Conditions," n.d.). The bronchioles lead up to the alveoli where oxygen from the air is absorbed into the blood. Carbon dioxide then travels from the blood to the alveoli where it is exhaled. Lungs are also covered by a thin layer of tissue (pleura) where it allows the lungs to contract and expand easily ("Anatomy and physiology of the lung - Canadian Cancer Society," n.d.).
Lung cancer is the most deadly cancer in the US and worldwide and causes more deaths than prostate cancer, breast cancer, and colon cancer combined. Since 1985, lung cancer has been the most common cancer worldwide with regard to incidence (which has increased by 51%) and mortality. It is estimated that worldwide there are 1,350,000 new cases of lung cancer every year which makes up 12.4% of all new cancer cases making it the largest contributor to new cancer diagnoses (Dela Cruz, Tanoue, & Matthay, 2011). Lung cancer is also the leading cause of death (1,180,000 deaths) amongst other cancers making up 17.6% of total cancer deaths (Dela Cruz, Tanoue, & Matthay, 2011). Lung cancer also ranks highest for estimated cancer deaths yearly at 85,600 (28% of all cancer deaths) for men and 71,340 (26% of all cancer deaths) for women. While survival advances have been made in other common cancers, this does not hold true for lung cancer which still only has a 5-year survival rate of 15.6% (Dela Cruz, Tanoue, & Matthay, 2011).
The approach of this paper will look into developing a proper drug delivery system (DDS) looking at a wide range of different types of cancers with previous DDS’s and creating one based on the following criteria: type of nanocarrier, effective delivery, shrinkage of tumor, distribution of drug, biocompatibility/chemical reactivity, and side effects. Some previous DDS’s used for a variety of types of cancers include inhalable magnetic nanoparticles, hyaluronic acid–ceramide nanoparticles, modified polypropylenimine (PPI) dendrimer, and stimuli-responsive clustered nanoparticles (Chang, Cho, Yi, Kim, & Jheon, 2016) (Shah et al., 2013) (Li et al., 2016) (Kulkarni et al., 2016). The approach of the DDS will include a hybrid composition of multiple nanocarriers types that will be at least dual layer.
Pathophysiology
The pathophysiology of cancer involves both environmental factors and genetic factors. Environmental factors involve carcinogenic factors such as tobacco smoking, viral infections, and ionizing radiations. For example, in the case of infections, general inflammation if the lung tissue may occur which results in the release of neutrophils (Aberle et al., 2011). Neutrophils may activate nitrogen species or reactive oxygen which end up binding to the DNA causing alterations in the genome. Inflammation is said to be an initiator of lung cancer development. In the course of cellular proliferation, errors may occur in chromosomal replication which may lead to further DNA mutation (Cooper, Lam, O’Toole, & Minna, 2013).
In genetics, lung cancer is initiated as a result of the inactivation of the genes of tumor suppression or activation of oncogenes. Mutation of K-ras proto-oncogene is responsible for 20-30% cell lung cancer. Damage in chromosomes may lead to the loss of heterozygosity which results in the inactivation of genes responsible for tumor suppression. Many genetic polymorphisms in gene coding are associated with lung cancer especially for apoptosis promoters, cytochrome P450, and interleukin-1(Goldstraw et al., 2011).
Healthy Lungs and Unhealthy Lungs
Clinical Outcomes
The most typical clinical outcome (50-70%) of lung cancer is a persistent cough due to the irritation of the cough receptors found along the airway due to the presence of a cancerous mass. A cough is more common in the case of squamous cell carcinoma. Obstruction of the central airway could cause further coughing due to distal atelectasis and post-obstructive pneumonia.
Hemoptysis is another clinical outcome that occurs when the tumor occupies the central airway. The blood vessels that develop as a result of tumor-induced angiogenesis are normally tortuous and leaky, making them highly vulnerable to rupture hence causing hemoptysis.
Weight loss also occurs as a result of the cancer-induced proteolysis and lipolysis which lead to loss of skeletal muscle and adipose tissue. A reduction in protein synthesis also occurs as a result of a cascade of some mechanisms brought about by the lung cancer hence contributing to generalized weight loss (Houghton, 2013).
Pleural effusion coupled with dyspnea and chest pain are also other clinical outcomes associated with lung cancer (Pao, Iafrate, & Su, 2011). Benign pleural effusion can occur due to atelectasis, post-obstructive pneumonia and lymphatic obstruction (when cancer becomes metastatic). On the other hand, malignant pleural effusion may occur when malignant cells can be found in the pleural fluid.
Epidemiology of Lung Cancer
Lung cancer is the leading cause of deaths by cancer in the United States and the world. After a review of recent data on lung cancer by Siegal and colleagues, it was found that an approximate total of 239,330 new cases of the disease and 161,240 deaths occurred in the United States as a result of Lung cancer (Ginsberg, Grewal, & Heelan, 2007). This is probably an underestimate of the true burden caused by lung cancer as it reflects data from 2007. It is the commonest cancer worldwide since 1985 regarding both mortality and incidence. In the global domain, it is the biggest contributor to new cancer diagnosis (about 1,350,000 new cases which represent 12.4% of the overall cancer cases) and cancer deaths (about 1,182,000 deaths which account for 17.6% of the total cancer deaths) (Detterbeck, Boffa, & Tanoue, 2009).
Currently, half of the cases (49.9%) occur in developing countries which were not the case back in the 1980s when 69% of the cases occurred in the developing countries (Risch & Plass, 2008). Lung cancer cases have increased by 51% since 1985 (with a 76% increase in women and 44% increase in men). In the US, lung, and bronchial cancer take the second position for both men and women with approximately 106,170 new cases in women (14% of new cases) and 115,160 new cases (14% of new cases) in men (Hoffman, Mauer, & Vokes, 2000).
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