Journal Article

Interplay between Smoking-induced Genotoxicity and Altered Signaling in Pancreatic Carcinogenesis

Navneet Momi, Sukhwinder Kaur, Moorthy P. Ponnusamy, Sushil Kumar, Uwe. A. Wittel and Surinder K. Batra

in Carcinogenesis

Volume 33, issue 9, pages 1617-1628
Published in print September 2012 | ISSN: 0143-3334
Published online May 2012 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgs186
Interplay between Smoking-induced Genotoxicity and Altered Signaling in Pancreatic Carcinogenesis

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Despite continuous research efforts directed at early diagnosis and treatment of pancreatic cancer (PC), the status of patients affected by this deadly malignancy remains dismal. Its notoriety with regard to lack of early diagnosis and resistance to the current chemotherapeutics is due to accumulating signaling abnormalities. Hoarding experimental and epidemiological evidences have established a direct correlation between cigarette smoking and PC risk. The cancer initiating/promoting nature of cigarette smoke can be attributed to its various constituents including nicotine, which is the major psychoactive component, and several other toxic constituents, such as nitrosamines, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, and polycyclic aromatic hydrocarbons. These predominant smoke-constituents initiate a series of oncogenic events facilitating epigenetic alterations, self-sufficiency in growth signals, evasion of apoptosis, sustained angiogenesis, and metastasis. A better understanding of the molecular mechanisms underpinning these events is crucial for the prevention and therapeutic intervention against PC. This review presents various interconnected signal transduction cascades, the smoking-mediated genotoxicity, and genetic polymorphisms influencing the susceptibility for smoking-mediated PC development by modulating pivotal biological aspects such as cell defense/tumor suppression, inflammation, DNA repair, as well as tobacco-carcinogen metabolization. Additionally, it provides a large perspective toward tumor biology and the therapeutic approaches against PC by targeting one or several steps of smoking-mediated signaling cascades.

Journal Article.  11640 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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