Oral Oncology 48 (2012) 383–392
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Ras oncogenes in oral cancer: The past 20 years
Avaniyapuram Kannan Murugan a,⇑, Arasambattu Kannan Munirajan b, Nobuo Tsuchida a,⇑ a b
Department of Molecular Cellular Oncology and Microbiology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai 600 113, India
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Oral squamous cell carcinoma (OSCC) of head and neck is associated with high morbidity and mortality in both Western and Asian countries. Several risk factors for the development of oral cancer are very well established, including tobacco chewing, betel quid, smoking, alcohol drinking and human papilloma virus (HPV) infection. Apart from these risk factors, many genetic factors such as oncogenes, tumor suppressor genes and regulatory genes are identiﬁed to involve in oral carcinogenesis with these risk factors dependent and independent manner. Ras is one of the most frequently genetically deregulated oncogene in oral cancer. In this review, we analyze the past 22 years of literature on genetic alterations such as mutations and ampliﬁcations of the isoforms of the ras oncogene in oral cancer. Further, we addressed the isoformspeciﬁc role of the ras in oral carcinogenesis. We also discussed how targeting the Akt and MEK, downstream effectors of the PI3K/Akt and MAPK pathways, respectively, would probably pave the possible molecular therapeutic target for the ras driven tumorigenesis in oral cancer. Analysis of these ras isoforms may critically enlighten speciﬁc role of a particular ras isoform in oral carcinogenesis, enhance prognosis and pave the way for isoform-speciﬁc molecular targeted therapy in OSCC. Ó 2011 Elsevier Ltd. All rights reserved.
Article history: Received 18 September 2011 Received in revised form 12 December 2011 Accepted 15 December 2011 Available online 11 January 2012 Keywords: HNSCC Ras mutation Oncogene Head and neck OSCC risk factors Oral cancer Ras signaling
Introduction Oral squamous cell carcinoma (OSCC) of the head and neck represent more than 90% malignancies arising in the head and neck anatomical region. This region includes malignant lesions arising from the lips, tongue, salivary glands, gingival, ﬂoor of mouth, oropharynx, buccal surfaces and other intra-oral locations.1,2 It is an increasing public health concern and represents one of the sixth most common cancers in the world. The prevalence of OSCC is different in various parts of the world, recent statistics indicate an annual incidence of 50,000 cases and 13,000 deaths in the US with relatively higher frequency and mortality in Africo-Americans.3,4 OSCC is currently ranked sixth in incidence and eighth in mortality for cancers in Europe.5 In general, OSCC is very common in Asia when compared to Western countries. The incidence is steadily increasing in Japan,6 it is highly prevalent in South and South-East Asia, comprising 40–50% of all the malignancies in India, Vietnam, Sri Lanka and other countries.7–13 The prevalence of OSCC differ greatly in different parts of the world, being attributed to the inﬂu⇑ Corresponding authors. Present addresses: Laboratory for Cellular and Molecular Thyroid Research, Division of Endocrinology and Metabolism, The Johns Hopkins University School of Medicine, 1915 East Madison Street, Suite 813 Hunterian Building, Baltimore, MD 21205, USA. Tel.: +1 410 502 3046 (A.K. Murugan); Department of Biosciences and Biotechnology, Kyushu University, Fukuoka 812-8581, Japan. Tel.: +81 92 642 4218 (N. Tsuchida). E-mail addresses: email@example.com (A.K. Murugan), firstname.lastname@example.org (N. Tsuchida). 1368-8375/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved....
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