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Rich66 · 06-02-2011, 08:28 PM

.Int J Med Sci. 2011 Mar 23;8(3):245-53.
Current status of methods to assess cancer drug resistance.

Lippert TH, Ruoff HJ, Volm M.

FREE TEXT

Source

Medical Faculty, University of Tübingen, Tübingen, Germany. Theodor-Lippert@web.de

Abstract

Drug resistance is the main cause of the failure of chemotherapy of malignant tumors, resistance being either preexisting (intrinsic resistance) or induced by the drugs (acquired resistance). At present, resistance is usually diagnosed during treatment after a long period of drug administration. In the present paper, methods for a rapid assessment of drug resistance are described. Three main classes of test procedures can be found in the literature, i.e. fresh tumor cell culture tests, cancer biomarker tests and positron emission tomography (PET) tests. The methods are based on the evaluation of molecular processes, i.e. metabolic activities of cancer cells. Drug resistance can be diagnosed before treatment in-vitro with fresh tumor cell culture tests, and after a short time of treatment in-vivo with PET tests. Cancer biomarker tests, for which great potential has been predicted, are largely still in the development stage. Individual resistance surveillance with tests delivering rapid results signifies progress in cancer therapy management, by providing the possibility to avoid drug therapies that are ineffective and only harmful.

PMID:: 21487568; [PubMed - in process]
PMCID: PMC3074090

J Med Chem. 2012 Apr 12;55(7):3113-21. Epub 2012 Mar 22.
Synthesis and Evaluation of (2-(4-Methoxyphenyl)-4-quinolinyl)(2-piperidinyl)methanol (NSC23925) Isomers To Reverse Multidrug Resistance in Cancer.

Duan Z, Li X, Huang H, Yuan W, Zheng SL, Liu X, Zhang Z, Choy E, Harmon D, Mankin H, Hornicek F.

LINK

Source

Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital , Boston, Massachusetts 02114, United States.

Abstract

Development of multidrug resistance (MDR) during chemotherapy is a fundamental obstacle associated with cancer care. Prior studies have identified (2-(4-methoxyphenyl)-4-quinolinyl)(2-piperidinyl)methanol (5) (NSC23925) to be a small molecule agent that reverses MDR in cancer cells. We synthesized all four isomers of 5 and analyzed them by liquid chromatography-mass spectrometry (LCMS). Structure-activity relationships for reversing MDR were evaluated. Isomer 11 demonstrated the most potent activity. 11 reversed MDR in several drug-resistant cell lines expressing Pgp, including ovarian, breast, colon, uterine, and sarcoma cancer. 11 resensitized these cell lines to paclitaxel, doxorubicin, mitoxantrone, vincristine, and trabectedin with no effect on cell sensitivity to cisplatin, topotecan, and methotrexate. 11 significantly enhanced in vivo antitumor activity of paclitaxel in MDR xenograft models, without increasing the level of paclitaxel toxicity. In conclusion, 11 and derivatives of this compound may hold therapeutic value in the treatment of MDR-dependent cancers.

PMID:: 22400811; [PubMed - in process]

06-02-2011, 08:28 PM	#3
Rich66 Senior Member Join Date: Feb 2008 Location: South East Wisconsin Posts: 3,431	Re: Chemoresistance .Int J Med Sci. 2011 Mar 23;8(3):245-53. Current status of methods to assess cancer drug resistance. Lippert TH, Ruoff HJ, Volm M. FREE TEXT Source Medical Faculty, University of Tübingen, Tübingen, Germany. Theodor-Lippert@web.de Abstract Drug resistance is the main cause of the failure of chemotherapy of malignant tumors, resistance being either preexisting (intrinsic resistance) or induced by the drugs (acquired resistance). At present, resistance is usually diagnosed during treatment after a long period of drug administration. In the present paper, methods for a rapid assessment of drug resistance are described. Three main classes of test procedures can be found in the literature, i.e. fresh tumor cell culture tests, cancer biomarker tests and positron emission tomography (PET) tests. The methods are based on the evaluation of molecular processes, i.e. metabolic activities of cancer cells. Drug resistance can be diagnosed before treatment in-vitro with fresh tumor cell culture tests, and after a short time of treatment in-vivo with PET tests. Cancer biomarker tests, for which great potential has been predicted, are largely still in the development stage. Individual resistance surveillance with tests delivering rapid results signifies progress in cancer therapy management, by providing the possibility to avoid drug therapies that are ineffective and only harmful. PMID: 21487568 [PubMed - in process] PMCID: PMC3074090 J Med Chem. 2012 Apr 12;55(7):3113-21. Epub 2012 Mar 22. Synthesis and Evaluation of (2-(4-Methoxyphenyl)-4-quinolinyl)(2-piperidinyl)methanol (NSC23925) Isomers To Reverse Multidrug Resistance in Cancer. Duan Z, Li X, Huang H, Yuan W, Zheng SL, Liu X, Zhang Z, Choy E, Harmon D, Mankin H, Hornicek F. LINK Source Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital , Boston, Massachusetts 02114, United States. Abstract Development of multidrug resistance (MDR) during chemotherapy is a fundamental obstacle associated with cancer care. Prior studies have identified (2-(4-methoxyphenyl)-4-quinolinyl)(2-piperidinyl)methanol (5) (NSC23925) to be a small molecule agent that reverses MDR in cancer cells. We synthesized all four isomers of 5 and analyzed them by liquid chromatography-mass spectrometry (LCMS). Structure-activity relationships for reversing MDR were evaluated. Isomer 11 demonstrated the most potent activity. 11 reversed MDR in several drug-resistant cell lines expressing Pgp, including ovarian, breast, colon, uterine, and sarcoma cancer. 11 resensitized these cell lines to paclitaxel, doxorubicin, mitoxantrone, vincristine, and trabectedin with no effect on cell sensitivity to cisplatin, topotecan, and methotrexate. 11 significantly enhanced in vivo antitumor activity of paclitaxel in MDR xenograft models, without increasing the level of paclitaxel toxicity. In conclusion, 11 and derivatives of this compound may hold therapeutic value in the treatment of MDR-dependent cancers. PMID: 22400811 [PubMed - in process]