Reviewing the oral carcinogenic process: key genetic events, growth factors and molecular signaling pathways (original) (raw)
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Cancer Prevention Research, 2020
Head and neck squamous cell carcinoma (HNSCC) was the 7th most common malignancy worldwide in 2018 and despite therapeutic advances, the overall survival rate for oral squamous cell carcinoma (OSCC; ∼50%) has remained unchanged for decades. The most common types are OSCC and oropharyngeal squamous cell carcinoma (OPSCC, survival rate ∼85%). Tobacco smoking is a major risk factor of HNSCC. In the developed world, the incidence of OSCC is declining as a result of tobacco cessation programs. However, OPSCC, which is also linked to human papillomavirus (HPV) infection, is on the rise and now ranks as the most common HPV-related cancer. The current state of knowledge indicates that HPV-associated disease differs substantially from other types of HNSCC and distinct biological differences between HPV-positive and HPV-negative HNSCC have been identified. Although risk factors have been extensively discussed in the literature, there are multiple clinically relevant questions that remain unan...
Clinical, pathological and molecular determinants in squamous cell carcinoma of the oral cavity
Future Oncology, 2010
Squamous cell carcinoma of the oral cavity (OCSCC) is the most frequently observed form of head-and-neck cancer in Southeast Asia and is the sixth most common cancer worldwide. Most cases of this preventable disease are caused by alcohol consumption, smoking and betel nut chewing. The survival rates of patients with advanced OCSCC have not increased significantly in recent years. While treatments for OCSCC are similar worldwide, survival rates differ by geographical area. The various genetic profiles and individual genetic susceptibility for carcinogens may account for this discrepancy. In some respects, molecular alteration or accumulation affects tumor progression and the clinical outcomes among patients with OCSCC. Clarifying the tumor behavior of oral cancer, with regard to pathological features or molecular aspects, could help clinicians to judge, tailor and adopt more effective therapeutic strategies to treat oral cancer.
Update of molecular pathobiology in oral cancer: a review
International Journal of Clinical Oncology, 2014
Head and neck cancer including oral squamous cell carcinoma (OSCC) is the sixth most common cancer in the world. OSCC has a high potential for local invasion and nodal metastasis, and the overall 5-year survival rate has not significantly changed during the past 30 years. Recent research has elucidated the detailed molecular mechanisms of carcinogenesis, tumor progression, and metastasis of OSCC. It is generally accepted that OSCC arises from multiple genetic alterations caused by chronic exposure to carcinogens such as alcohol, smoking, viral infections, and inflammation. The molecular mechanisms of carcinogenesis, tumor progression, and metastasis of head and neck cancer have been elucidated by recent advances in molecular biology. However, many unsolved questions remain. In this review, we describe the current molecular biological findings such as human papillomavirus infection, epithelial-mesenchymal transition, microRNA, and our novel molecular pathological findings of OSCC.
UNIVERSITY JOURNAL OF DENTAL SCIENCES
Oral carcinogenesis is known as multifactorial process which engaged plentiful genetic events that transform normal activity of tumor suppressor genes and oncogenes. It is observed that aggregation of genetic alterations is the ground for advancement of a normal cell to cancer cells, which is known as a multi-step carcinogenesis. Because of this event, growth factor production increases as well as increase in total of receptors on cell surface and increased intracellular signal messengers. The present review scrutinize the existing documentation in the literature related to the oral squamous cell carcinoma. English language articles were searched in various databases such as Pubmed, Scopus, Science direct and Google scholar. The keyword used for searching are “oral squamous cell carcinoma”, “Genetics and Oral squamous cell carcinoma”,“Molecular mechanism in oral squamous cell carcinoma”. The present review spotlights on understanding the molecular mechanism and the genetic factors ...
Role of Smoking-Mediated molecular events in the genesis of oral cancers
Toxicology Mechanisms and Methods, 2019
Smoking is a pernicious practice prevalent worldwide. It involves breathing of burnt-tobacco fumes/smoke which comprises of numerous chemical entities posing deleterious aftermaths in the oral cavity. Tobacco fumes carry carcinogens namely damaging chemicals like nitrosamines, polycyclic aromatic hydrocarbons, aldehydes, nicotine, phenols, carbon monoxides, radioactive elements, heavy metals ions. Oral cavity (mouth or buccal cavity), forming initial contacts with tobacco smokables, plays an essential role in the digestive system, facial determinations and speech. Smoking is a significant risk factor for oral cavity cancers. Nearly 50% of deaths from oral cavity cancer (oral cancer) attribute to smoking. This review intends to focus on the smoking mediated molecular modulations that are associated with the genesis of oral cancers. A c c e p t e d M a n u s c r i p t functional abilities are determined by the three-dimensional structure which in turn depends on the amino acids sequence and post-translational modifications (figure 1) (Crick 1970; Lin and Elowitz 2016). Smoking induces multitude aberrations in the molecular components of cells (the fundamental unit of life), ultimately disrupting the physiological homeostasis of the oral cavity (Shwetha et al. 2018). The DNA and cellular constitute of healthy oral mucosa are constant while in smoking addicts cells exhibit chromosomal, genetic and epigenetic abnormalities (Khowal et al. 2018b). During cell division, T_Sm mediated mutations are passed on to daughter cells and mutations guided fate of T_Sm exposed oral cells is followed (Lin and Elowitz 2016). This review focuses on the smoking mediated molecular modulations that are associated with the genesis of oral cancers. 2. Oral cavity cancer Cancer is a multi-factorial, complex genetic disorder. The cancer genome accumulates more and more abnormalities/mutations during tumor initiation, progression and metastasis (Bijanzadeh 2017). Though the exact genetic routes responsible for malignant transformation, are still unknown, few key attributes having concordance with cancer initiation and progression have been realized lately (Loaiza and Demaria 2016). The vital molecular characteristics favoring carcinogenesis comprises of abundant proliferative signals, circumvented growth suppressors, abstained apoptosis, abnormal cells with replicative immortality, angiogenesis and vascularisation of nascent tumors, and invasion & metastasis (Hanahan and Weinberg 2011). Cancers commonly arise in cellular/tissue microenvironments struggling from chronic built-up of oxidative and inflammatory stresses (Hanahan and Weinberg 2011). Carcinogenesis is preceded by a non-life threatening phase, with reversible pathological attributes and molecular aftermaths, termed as the pre-malignant or potentially malignant or pre-cancerous condition (Ryan and Faupel-Badger 2016); medical interventions executed during precancerous period are less stringent and show higher survival rates than the treatment strategies implemented during the cancerous period or phase of a lesion (Maza et al. 2017). The early stage diagnosis of pre-cancer and cancer lesions is crucial for determining the disease outcome; moreover, majority of cancer cases prove fatal because of diagnosis at higher/more-severe tumor grade and stage (Field and Youngson 2002). Oral cavity cancer or oral cancer is a serious life-threatening global pandemic affecting human health and lifestyle worldwide (Kampman et al. 2018). Oral cancer, a subgroup of head and neck cancers, has shown alarming prevalence globally, affecting both more developed and less developed countries. More than 90 percent of oral A c c e p t e d M a n u s c r i p t cancer cases are diagnosed as oral squamous cell carcinoma (OSCC) which are malignant lesions arising from the epithelial lining of the oral mucosa (Cameron Goertzen et al. 2018). OSCC lesions are comprised of abnormal cells showing non-regulated or uncontrolled cell divisions; the tissue surrounding cancerous loci constitutes tumor microenvironment that plays an important role in cancer sustenance, progression and immune system evasion (Nieh 2017). The oral pre-cancer (pre-malignant) conditions are major risk factors for OSCC. The oral pre-cancer conditions are indicative of epigenetic and genetic abnormalities which, in comparison to the normal/healthy physiology, pre-disposes the lesion for advancement towards malignant or cancer associated epigenetic and genetic abnormalities. The commonly diagnosed oral pre-cancer conditions include leukoplakia, erythroplakia, erythroleukoplakia and oral lichen planus (Yardimci et al. 2014; Thomson 2015). Leukoplakia is thick, white colored patch appearing in the diseased oral mucosa. Erythroplakia and erythroleukoplakia are conditions where red and red-white (mosaic) colored patches are seen respectively within the unhealthy oral cavity. Oral lichen planus, the oral pre-cancer chronic inflammatory disorder, results in bilateral white striations or plaques within the oral cavity (Deshpande 2017). Erythroplakia lesions have a strong probability of malignant transformations (Speight et al. 2017). The main etiological factors associated with oral carcinogenesis include chronic habits for the intake of tobacco, areca nut and alcoholic products (alone or in combinations) (Kumar et al. 2016; Yenugadhati et al. 2018). By various epidemiological studies, tobacco (smokable or chewable) is the primary etiology for oral cancer incidences
Divergent routes to oral cancer
Cancer research, 2006
Most head and neck squamous cell carcinoma (HNSCC) patients present with late-stage cancers, which are difficult to treat. Therefore, early diagnosis of high-risk premalignant lesions and incipient cancers is important. HNSCC is currently perceived as a single progression mechanism, resulting in immortal invasive cancers. However, we have found that approximately 40% of primary oral SCCs are mortal in culture, and these have a better prognosis. About 60% of oral premalignancies (dysplasias) are also mortal. The mortal and immortal tumors are generated in vivo as judged by p53 mutations and loss of p16(INK4A) expression being found only in the original tumors from which the immortal cultures were derived. To investigate the relationships of dysplasias to SCCs, we did microarray analysis of primary cultures of 4 normal oral mucosa biopsies, 19 dysplasias, and 16 SCCs. Spectral clustering using the singular value decomposition and other bioinformatic techniques showed that development ...
A Short Review of the Role of Genetic in Oral and Squamous Cell Carcinoma
2020
This review aimed to analyze the role of genetic in oral cancer. Head and Neck cancer is multifactorial disease in which a wide factors play a role in its apparition and progress. More than 90% of malignant neoplasms are oral squamous cell carcinoma developed on the mucous epithelium and the sixth most common cancer in the world. The environment, such as smokeless tobacco, alcohol, betel quid chewing are most common factors are involved in the etiology of the oral cancer. Several genes and pathways associated with oral squamous cell carcinoma are significant in terms of early detection and prognosis. Molecular biomarkers are being discovered in oral cancer diagnostic. It could be used as screening for detection and improve therapeutic strategies of oral pre-cancer and oral squamous cell carcinoma.