P53: The Leading Cause Of Lung Cancer

In the past years, there has been a major paradigm shift in the management of non-small cell lung cancer also known as (NSCLC). NSCLC should now be further sub-classified by histology and driver mutation if one is known or present. Translational research results now allow such mutations to be inhibited by either receptor monoclonal antibodies (mAb) or small molecule tyrosine kinase inhibitors (TKI). Whilst empirical chemotherapy with a platinum-doublet remains the gold standard for advanced NSCLC without a known driver mutation, targeted therapy is pushing the boundary to significantly improve patient outcomes and quality of life. In this review, we will examine the major subtypes

An irritant, such as cigarette smoke, effects the cells of the epithelium lining. Initially the body can repair the cell, but with repeated exposure the cells of the lungs become damaged and grow uncontrollably. P53 is a gene for various downstream targets that are involved in cell progression, DNA repair and regulation of cells that undergo apoptosis. Mutations to P53 hinder its normal tumor suppressing capabilities. Therefore, DNA damage remains unchecked, faulty cells proceed through the cell cycle and apoptosis is invaded. All these factors create a genetic condition where the cell is more susceptible to further mutation. If the cancer grows large enough, it can affect the organ by closing off the aveoli, leading to shortness of

Non-small cell lung cancer (NSCLC) represents 85% of lung cancer case1,2. Due to metastasis and other individual conditions, only 30% of the patients are able to go for a surgery, the best regarded treatment method2. Others predominately use tradition chemo- and radio-based therapeutic methods, which held poor treatment outcome with only 15% of the patient lives longer than 5 years1. However, since the establishment of RNAi therapy in 1998, the efficacy of RNAi on tumour activity related genes was intensively studied and some research trials has shown potential effects in treating NSCLC by this method1-3.

More than four thousands mutations of p53 genes have been identified in human tumors. p53 mutation in human skin cancers is consider to be unique mutation among other cancers mutations. p53 mutation in human skin cancers is mostly found to be C to T transitions. These transitions are located on dipyrimidine sites that are the specific target for UV radiation (Dumaz et. al, 1997). Alteration of tumor suppressor gene p53 will hinder p53 to repair damaged DNA or perform apoptosis as needed, which then results in precancerous cell (Madan et. al,

First the p53 protein would need to be isolated. The simplest method for identifying proteins that bind to one another tightly is co-immunoprecipitation. In this technique, an antibody is used to capture and precipitate a specific target protein from an extract prepared by breaking open cells. If p53 is associated tightly with another protein, the partner protein will precipitate as well. Use antibodies against p53

Due to its potent tumor suppressive activity, a molecular understanding of p53 action will create significant experiences into specific procedures that limit tumor growth and may identify key

2 out of 5 cancer cases are lung cancer. Furthermore, a quarter of all the cancer deaths come from lung cancer. In this current year, 158,040 people are estimated to die from this cancer, (ALA, n.d). Those people have one type of lung cancer; whether it is non-small or small cell, but non-small cell is the most common diagnosed type. This disease can emerge from the lungs and develop, or spread into the lungs from other organs. The most common pathogen that triggers lung cancer is smoking cigarettes. However, other catalysts can trigger it too. This cancer is latent in some cases, but when it becomes active, the syndromes that are in the chest, infrequent to occur, and deteriorating are signs that have to get medical attention. These symptoms can happen with other illnesses, too. However, noticing these symptoms, the person should talk to a doctor, who can help find the cause and the appropriate treatment from the four main treatments. The bright side of this disease that the people’s awareness has increased; as a consequence, the lung cancer cases are feasibly decreasing

The p53 is a vital tumour suppressor protein in humans which is important for cell cycle regulation. Ablation of the p53 protein causes the cell to proliferate infinitely that contributes to the development of tumours. Through the cell-autonomous program the cell-cycle arrest and apoptosis is caused by the presence of p53. The aim of the journal is to study cellular senescence program in hepatic stellate cells that is p53-dependent which is formed by dying hepatocytes which secret factors that influence the tissue microenvironment, preventing fibrosis, cirrhosis and liver cancer via promoting p53 senescent in these HSCs. The research objectives explain that fibrosis is limited through the p53-mediated senescence program by stopping HSC proliferation through cell-autonomous canonical senescence regulators and the non-cell-autonomous effects of SASP on ECM and immune surveillance. Currently there is a debate on the role p53 plays in HSCs which influences later stages of liver cancer and the research exhibits that through non-cell-autonomous mechanisms, p53 can inhibit cancer by manipulating the tissue microenvironment.

The 2015 WHO classification of lung tumours (add ref) was used to categorise biopsies by the predominant histological subtype. Of 274 cases, 167 (61%) were acinar predominant adenocarcinomas, 63(23%) solid adenocarcinomas, 19 (7%) invasive mucinous adenocarcinomas, 11(4%)lepidic predominant, papillary 9 (3.30%), two cases each of colloid (0.7%) and non- small cell carcinoma, not otherwise specified (NSCC-NOS) (0.7%) and one micro-papillary predominant subtype (0.3%) (Figure 1; Figures 2A-2D; Figures 3A-3D).

When p53 is lost due to mutation, it can lift the sanctions on cell division and growth. Because cancer causes most of its damage through uncontrolled growth, it makes sense that many of them have a mutated p53.

All cancerous tumors have a basic structure of a large group of cells with a small cluster of cells in the center of the tumor that are responsible for the growth and recurrence of cancer. These central cells are the most difficult part of the tumor to destroy. Mutations in tumor suppressor genes are essential for promoting and allowing tumors begin forming, through spontaneous or even hereditary forms of cancer (Collins, 1997). Cancer is caused by mutation in genes, however not all mutations can cause cancer but certain combinations of genetic mutations do cause cancer (Blanpain, 2015). Cancer cells are cells that divide uncontrollably due to mutations in genes; the mutations in oncogenes and tumor suppressor genes largely affect the aggressiveness of cancer (Yokota, 2000). Through lots of research it has been proven that cancers are heterogeneous and show different functions and phenotypic traits at cell level

The p53 (protein having a molecular weight of 53 (kilodaltons) is a hereditary gene concerned with Li-Fraumeni Syndrome, a condition that involves development of independent tumor within the body tissue. The tumor protein accounts on all general human genes. P53 protein is believed to be among the unifying factor in cancer disease. Its activity alters the formation of tumors by compressing them. The activities may at times result to uncontrolled cell divisions creating risks for DNA genes. When the suppression activities are disabled, a person experiencing gene mutation is prone to cancer disease. P53 mutations within the body tissue enhance the tumor formation by modifying the molecular networks and increasing the mutagenic effects. Its protein bind stimulates the formation of p21, which in turn associates with the cell division stimulating protein (cdk2). The process of cell division is thereby stopped as the p21 composited with the cdk2 cannot facilitate the next stage of cell division. This creates a path way for the division and formation of tumors as the p21 proteins are inadequate. Thus, p21 is regarded as a component for terminating tumor formation.

p53 gene, also known as tumor protein 53 (TP53), encodes for a tumor suppressor protein which regulates the cell cycle and apoptosis. The p53 protein has been described as the guardian of the genome (1) because of its role in preventing genetic mutation. It belongs to a protein family which includes p53, p63 and p73 and these are structurally and functionally related to each other. However, p53 seems to have evolved as a tumor suppressor in higher organisms, while p63 and p73 play a role in normal developmental biology (2).

Lung cancer is a dangerous health problem which affects many people (Thomas, 2013). It becomes the top killer among other types of cancers in the world (Molina, Yang, Cassivi, Schild & Adjei, 2008). According to the statistics made by National Institute of Health, more than 161, 000 cases were reported in U.S. involving death caused by lung cancer in 2008 (Samet, Tang, Boffetta, Hannan, Marston, Thun et, al., 2009). Despite the decreasing trends of lung cancer incidence rates for men in the 1980s and for women in the late 1990s, still the lung and bronchus cancer remain the significant cause of cancer mortality in the United States, with an estimation of 87,750 and 72,590 deaths to occur in men and women, respectively, in 2012 (Field & Withers, 2012)

Cancer is a major cause of mortality: more than ten million people are diagnosed with the disease annually. Cancer is known to develop via a multistep carcinogenesis process entailing numerous cellular physiological systems such as cell signaling and apoptosis, making it a highly incomprehensible and complex disease [1,2]. Initially, cancers start as localized diseases, but they are prone to spread to distant sites within the body, which makes cancer incurable. To date, cancer treatments have been performed on the basis of clinical and pathologic staging that is determined using morphologic diagnostic tools, such as conventional radiological and histopathological examinations. The most common cancer treatments are restricted