Introduction

Epidemiology and Etiology of Lung Cancer

The incidence and prevalence of lung cancer is increasing worldwide, with the prevalence estimated to almost double by 2040 and it is second leading cause of death [1]. As indicated by current information of GLOBOCAN 2018, Lung carcinoma shows that 11.6% of a wide range of cancer, out of which 80% were ascribed to smoking, natural air contamination caused 108,000 lung cancer death as reported in [2]; solid fuels used more in developing countries for cooking and heating caused 36,000 lung cancer deaths [3]. Global patterns show that for men and women consolidated, almost 50% of the new cases and the greater part of the malignant growth deaths worldwide in 2018 are evaluated to happen in Asia, in part because the region has nearly 60% of the global population. Lung malignant growth is the most normally analyzed disease in men (14.5% of the complete cases in men and 8.4% in women) and the main source of disease death in men (22%, i.e., about 1 in 5 of all cancer deaths) and in women (13.8%). A WHO report said that at least 1.7 million cancer deaths annually could be reduced through healthy working and living environments [4].

Biology of Lung Cancer

Lung cancer growth can emerge in any piece of the lung, yet almost 90% of it is thought to emerge from the epithelial cells lining the airways; and consequently, lung cancer is sometimes called Bronchogenic carcinoma. Cancer arising from the pleura is called mesothelioma. An age more than 65, active or passive smoking, introduction to asbestos fibers and radon gas, lung infections, air contamination and a family ancestry of lung tumor growth, are risk factors for this condition. Basic histological classification of lung cancer; because of differences in their biological behavior, the distinction between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) is important. NSCLC is additionally separated into Adenocarcinoma, Squamous cell carcinoma and large cell carcinoma. Lung malignant growth is exceptionally heterogeneous that can emerge in various sites in the bronchial tree, in this manner presenting many factor symptoms and signs relying upon its anatomic area. Lung disease has no genuine early symptoms, so it is regularly possibly analyzed when it has arrived at an advanced stage (stage III or IV). Normal lung tumor symptom includes persistent cough, blood in the sputum, repeated respiratory infections, chest pain, unexplained weight reduction, weakness and shortness of breath [5].

Metabolism of Lung Cancer

Metabolism envelops the biochemical procedures that permit healthy cells to keep vitality, redox balance and building blocks required for cell growth, survival and proliferation consistent. Tumor cells are all around reported to reprogram their energy production and metabolic systems to help quick proliferation and survival in harsh conditions through mutations in oncogenes and inactivation of tumor suppressor genes. The metabolic changes of tumor cells, that recognize them from healthy cells, are perceived as one of the ten signs of malignant growth [6]. An altered metabolism causes malignant growth of cells to continue high proliferative rates even in a threatening situation coming about because of a poor vascularization, which restrains the supply of oxygen (O₂) and essential nutrients [7]. During the 1920s, Otto Warburg proposed that tumor cells devour glucose and discharge lactate at a fundamentally higher rate contrasted with solid resting cells. Indeed, even in incompatible conditions, proliferating cells, for example, disease cells, depend on maturation, i.e., glycolysis bringing about the generation of lactate through fermentation of pyruvate. The expanded decrease of pyruvate to lactate and the section of glycolytic intermediates into different biosynthetic pathways decrease the available concentration of pyruvate to frame acetyl-CoA and to drive the tricarboxylic corrosive (TCA) cycle. Interestingly with the first hypothesis of Warburg, the mitochondrial metabolism stays fundamental for both the creation of ATP and the supply of biosynthetic intermediates [8]. Lung tumor cells frequently harbor transformations in genes and pathways, for example, the PI3K (phosphoinositide-3-kinase)-AKT-mTOR (mammalian objective of rapamycin) pathway, the oncogenes RAS, c-MYC, and HIF-1 (hypoxia inducible factor), and the tumor silencer gene TP53 (tumor protein). These cells signaling pathways are implicated in the metabolism by safely directing the limit of cells to acquire access to supplements and hence process these compounds [12].

RAS-RAF-MEK-MAPK Pathway

Activation of RAS proteins at the cell membrane by development factors brings about the official of effector molecules, formation of signaling complexes and initiate of a course of intracellular signaling pathways including the RAS-RAF-MEK-MAPK-and PI3K-AKT-mTOR pathway. RAS proteins shift back and forth among GTP-and GDP-bound conformation, where the GTP-bound conformation represents the dynamic state. Oncogenic mutates function by restricting hydrolysis of GTP, along these lines producing highly active RAS molecules bringing about uncontrolled development and malignant change. Initiating (K)RAS mutations are pervasive in ~15–20% of NSCLC and 30–50% of the adenocarcinoma subtype [9]. The RAS family encodes four-layer bound proteins that are engaged with signal transduction hidden assorted cell exercises, for example, differentiation, development, migration, proliferation, and survival [13].

HIF-1

In hypoxia, prolyl-dehydroxylases are inert as they require O2 as a basic cofactor. In the nucleus, the stabilized HIF α-subunit dimerizes with HIF-1β and incites the transcription of numerous qualities engaged with proliferation, apoptosis, and angiogenesis. HIF-1 articulation is missing in healthy lung tissue conversely with malignant lung tissue, where increasing degrees of HIF-1 are recorded [11]. The transcription factor HIF is a heterodimeric complex made out of a unstable oxygen-subordinate α-unit and a steady oxygen-unsensitive β-unit. Under ordinary O2 conditions, the α-subunit of HIF is hydroxylated by prolyl dehydroxylases, permitting recognition and ubiquitination by the Von Hippel Lindau ubiquitin ligase, which marks them for fast degradation [14].

c-MYC

The MYC proto-oncogene individuals are targets of RAS and PI3K-AKT-mTOR signaling and basic controllers of various downstream pathways, for example, apoptosis, differentiation, and multiplication. The MYC oncogene family is every now and again deregulated in both NSCLC and SCLC. Activation of MYC individuals regularly happens through amplification although overabundance MYC expression can likewise result from retroviral promotor inclusion, chromosomal translocation, activation of enhancers inside the MYC gene or mutations of upstream signaling pathways that upgrade MYC stability [15]. Concerning metabolic reprogramming, the cMYC transcription factor advances expression of glycolytic target genes (GLUT, HK, PFK1, and ENO) and LDH contributing straightforwardly to the Warburg impact [16].

TP53

In lung carcinoma, TP53 is an ordinarily inactivated tumor silencer gene. TP53 encodes a protein, p53 that prevents the collection of genetic damage during mitosis. Because of cell stress, p53 incites the statement of genes that manage cell cycle checkpoints, coming about in G1 arrest and DNA repair or apoptosis. Wild type TP53 inhibits transcription of glucose transporters, promotes the expression of Tumor Protein 53-Induced Glycolysis and Apoptosis Regulator (TIGAR), and inhibits the transcription of glycolytic catalysts like PGM [17].

Results and Discussion

Lung cancer is the second most successive cancer in both sexes. The significant hazard factor for lung cancer is smoking, which represents 75-80% of lung cancer-related passing’s. Lung cancers can be extensively characterized into two structures, little cell carcinomas and non-little cell carcinomas. Non-little cell lung cancer is increasingly normal, representing up to 75% of lung cancers. Lung cancer is analyzed by chest radiography, sputum cytology, bronchoscopy, needle biopsy, and different strategies. Adjuvant chemotherapy may give a little endurance time advantage if the routine incorporates cisplatin. Chemotherapy joined with radiation treatment may deliver an endurance advantage over illumination alone. Patients with cutting edge non-little cell lung cancer ought to get mix chemotherapy. A few regimens have indicated an endurance advantage over best steady consideration. Docetaxel, Paclitaxel, Gemcitabine and Topotecan have action both as single operators and in blend. Medical procedure has just a constrained job in the administration of little cell lung cancer. Chemotherapy ought to be offered to patients with broad illness. The most dynamic regimens contain cisplatin or carboplatin. Lung cancer, albeit exceptionally preventable, is generally analyzed at a serious stage. Chemotherapy is assuming an inexorably significant job nearby medical procedure and radiation treatment in the administration of this ailment. In this review, biological mechanism and metabolism is mentioned to understand the concept of Lung Carcinoma processing in human body and what cell signals do play role with factors to restrict or initiate them.

CONCLUSION

In developed countries, for example, the UK and the US, lung malignant cancer mortality is declining and a high survival rate has been accomplished, likely because of awareness programs and blooming medical technologies but in developing countries, for example, India and Egypt, sufficient efforts are required to reduce mortality due to lung cancer. This review paper shows recent discoveries identified with key transcription factors and enzymes that assume a significant contribution in the regulation of lung cancer metabolism. Metabolic unsteadiness caused by environmental impacts or improper function of specific enzymes and substrates may bring about transformations in oncogenes and tumor suppressor genes, which leads to activate or inhibit the signaling pathways and transcription factors which represent the metabolic reprogramming observed in malignant cancer cells. These metabolic changes are obligatory for the necessities of quickly proliferating cells: a fast ATP generation to keep up energy status, an increased synthesis of biomolecules and to maintain the redox balance in cells.

ACKNOWLEDGEMENT

The author wishes to acknowledge Prof. Kamlesh Choure, Head of Department of Biotechnology, AKS University, Satna for providing necessary facility and scientific platform.

CONFLICT OF INTEREST

The author declares no conflict of interest.