Abstract Detail

Abstract

Oral cancer is an aggressive tumor whose biological activity is not limited to an uncontrolled proliferative state, as traditionally believed, but also has other complex abilities and interactions that go beyond a simple hyperproliferative state. Although advances in cancer research have provided a wealth of new information about the cellular processes and molecular biology underlying oral carcinogenesis and tumor progression, the treatment and management of complications and local recurrence result in high morbidity and mortality, especially when the disease has evolved over time. Ongoing molecular trends show that Oral squamous cell carcinomas may not be considered as homogenous as previously supposed. We have investigated trends in various molecular pathways of oral cancer and precancer cases in Indian population which have shown an array of alterations such as increased and altered expression of p53, activating mutations of H-ras oncogene, increased Bcl-2 and Survivin expression (antiapototic markers), decreased E-cadherin expression (cell adhesion molecule), increased GLUT-1 (glucose transporter) and VEGF expression at the invasive front of oral cancer. A determining aspect in the Epithelial mesenchymal transition(EMT) is the loss of E-cadherin expression, an adhesion molecule essential for holding epithelial cells together in clusters that hinder their motility and promotes invasion and metastatic spread. The mechanisms by which EMT is established are essentially due to the actions of certain transcription factors (Twist), which activate genes responsible for the events that unfold in epithelial cells during EMT. In our studies we have also highlighted the importance of the RB1 tumor suppressor as a target for cancer therapy. RB1 regulates cell cycle progression and represents the downstream target for cyclin-dependent kinase inhibitors that are in clinical use. However, newly discovered features of the RB1 pathway suggest new therapeutic strategies to counter resistance and improve precision medicine. Subsequently, we have also deduced the role of inflammation, in conferring aggressiveness to a tumor, which is also regarded as a fundamental process in the evolution of the Tumor Microenvironment. NK cells in advanced neoplasms have an anergic phenotype, meaning that they are unable to secrete INF-γ and kill tumour cells. In the initial phases of the neoplasm, in which the tumour cells have not yet acquired the capacity to secrete TGF-β, NK cells could fully exert their anti-tumour effector functions. All these molecular changes have indicated complex alteration leading to a genetically altered cell line which is responsible for development of oral malignancy. Our research in recent years has led to an optimistic diagnostic and therapeutic approach based on a clearer understanding of the molecular basis of oral cancer development and progression. It has also provided interesting insights into early carcinogenic changes in potentially malignant oral diseases and their malignant transformation.Large-scale studies with different biomarkers are needed to obtain evidence-based results affecting different characteristics of oral cancer in order to modify current treatment regimens. Audience Take Away • Basic to advanced chair side investigation for oral premalignancy and malignancy would benefit the practioners in bridging the gap between knowledge and practice. • Comprehensive molecular pathogenesis will highlight the various diagnostic and prognostic modalities for oral premalignancy and malignancy.

Biography

Dr. Devi Charan Shetty is an avid Oral Pathologist, heading the Department of Oral Pathology & Microbiology and Forensic Odontology at I.T.S. Dental College, Ghaziabad and is presently the Director-Principal of the institute.Dr. Devi Charan Shettyhas been a key note speaker at various national and international level forums on Oral Cancer & Molecular Pathology concepts.Dr. D.C Shetty has published more than 100 papers in peer reviewed indexed scientific journals of National and International repute.Dr. Shettyhas been instrumental in overseeing the Centre for Advanced Research at I.T.S Dental College, Ghaziabad, which is equipped with the state of the art equipments such as PCR, ELISA, Immunohistochemistry, Gel electrophoresis and Spectrophotometry.