Journal ArticleDOI
Molecular basis of cellular response to cisplatin chemotherapy in non-small cell lung cancer (Review)
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TLDR
In this review, insights are provided into the pathways involved in cisplatin damage from entering the cells to execution of apoptosis or survival of NSCLC cells and this knowledge should provide a basis for further studies to improve the understanding of molecular events associated with lung cancer.Abstract:
Cisplatin is one of the most potent anticancer agents, displaying significant clinical activity against a variety of solid tumors. For more than two decades, the most effective systemic chemotherapy for non-small cell lung cancer (NSCLC), the leading cause of cancer morbidity and mortality among men and women in the western world, was cisplatin-based combination treatment. Unfortunately, the outcome of cisplatin therapy on NSCLC seems to have reached a plateau. Therefore, the biological mechanisms of cisplatin action need to be understood in order to overcome the treatment plateau on NSCLC. Moreover, the development of resistance is a hurdle in the use of this drug. The molecular mechanisms that underlie this chemoresistance are largely unknown. Possible mechanisms of acquired resistance to cisplatin include reduced intracellular accumulation of cisplatin, enhanced drug inactivation by metallothionine and glutathione, increased repair activity of DNA damage, and altered expression of oncogenes and regulatory proteins. In addition, it is generally accepted that cytotoxicity of cisplatin is mediated through induction of apoptosis and arrest of cell cycle resulting from its interaction with DNA, such as the formation of cisplatin-DNA adducts, which activates multiple signaling pathways, including those involving p53, Bcl-2 family, caspases, cyclins, CDKs, pRb, PKC, MAPK and PI3K/Akt. Increased expression of anti-apoptotic genes and mutations in the intrinsic apoptotic pathway may contribute to the inability of cells to detect DNA damage or to induce apoptosis. Towards an understanding of the molecular basis of the cellular response to cisplatin-based chemotherapy in NSCLC, in this review we provide some insights into the pathways involved in cisplatin damage from entering the cells to execution of apoptosis or survival of NSCLC cells. We believe that as more and more molecular mechanisms of response to cisplatin-based therapy are unraveled, this knowledge should provide a basis for further studies to improve our understanding of molecular events associated with lung NSCLC as well as to devise novel and effective therapeutic approaches to overcome the treatment plateau or reverse drug resistance in this disease.read more
Citations
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Journal ArticleDOI
Nuclear drug delivery for cancer chemotherapy
TL;DR: The biological barriers and recent progress of nuclear drug delivery for cancer chemotherapy are discussed and strategies that appear useful for design of vehicles capable of delivering drugs to the nucleus are emphasized, particularly for in vivo applications.
Journal ArticleDOI
Chrysin protects against cisplatin-induced colon. toxicity via amelioration of oxidative stress and apoptosis: Probable role of p38MAPK and p53
Rehan Khan,Abdul Quaiyoom Khan,Wajhul Qamar,Abdul Lateef,Mir Tahir,Muneeb U. Rehman,Farrah Ali,Sarwat Sultana +7 more
TL;DR: The results of the present study suggest that the protective effect of chrysin against CDDP-induced colon toxicity was related with attenuation of oxidative stress, activation of p38MAPK and p53, and apoptotic tissue damage.
Journal ArticleDOI
Epigenetic inactivation of the putative DNA/RNA helicase SLFN11 in human cancer confers resistance to platinum drugs
Vanesa Nogales,William C. Reinhold,Sudhir Varma,Anna Martínez-Cardús,Catia Moutinho,Sebastian Moran,Holger Heyn,Ana Sebio,Agustí Barnadas,Yves Pommier,Manel Esteller,Manel Esteller +11 more
TL;DR: This work has used a comprehensive DNA methylation microarray platform to interrogate the widely characterized NCI60 panel of human cancer cell lines with respect to CpG methylation status and cisplatin/carboplatin sensitivity and identified SLFN11 epigenetic inactivation as a predictor of resistance to platinum drugs in human cancer.
Journal ArticleDOI
Hyperactive EGF receptor, Jaks and Stat3 signaling promote enhanced colony-forming ability, motility and migration of cisplatin-resistant ovarian cancer cells
Peibin Yue,Xiaolei Zhang,David Paladino,Bhaswati Sengupta,Sarfraz Ahmad,Robert W. Holloway,Susan B. Ingersoll,James Turkson +7 more
TL;DR: Hyperactive EGFR signaling through Stat3 and the Jak-Stat3 activity together promote ovarian cancer progression to cisplatin resistance and therefore represent targets for preventing the development of cisplatins resistance and the recurrent disease during cis platin therapy in ovarian cancer.
Journal ArticleDOI
Up-regulation of 14-3-3ζ in lung cancer and its implication as prognostic and therapeutic target
Tao Fan,Ruiyun Li,Nevins W. Todd,Qi Qiu,Hong-Bin Fang,Huijun Wang,Jianjun Shen,Richard Y. Zhao,Nancy P. Caraway,Ruth L. Katz,Sanford A. Stass,Feng Jiang +11 more
TL;DR: The results suggest that 14-3-3zeta is a potential target for developing a prognostic biomarker and therapeutics that can enhance the antitumor activity of cisplatin for NSCLC.
References
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BookDOI
Cisplatin : chemistry and biochemistry of a leading anticancer drug
TL;DR: The start: platinum complexes for the treatment of cancer - why the search goes on and new developments: structure-activity relationships within di- and trinuclear platinum phase I clinical anticancer agents the development of orally-active platinum drugs methods for screening the potential antitumor activity of platinum compounds in combinatorial libraries computational studies on platinum antitumors complexes and their adducts with nucleid acids constituents.
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Molecular Aspects of Anticancer Drug-DNA Interactions
Stephen Neidle,Michael J. Waring +1 more
TL;DR: The cellular and molecular pharmacology of the anthrapyrazole antitumour agent and the mitomycins - natural cross-linkers of DNA, M.D. Wilson and F.A. Tomasz are studied.
Journal ArticleDOI
Piecing Together the p53 Puzzle
TL;DR: New findings showing that the checkpoint kinase CHK2 regulates a crucial central player in checkpoint pathways-the tumor suppressor protein p53 are discussed.