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Drug Combinations to Enhance Therapeutic Efficacy and Edit Out Side Effects and Resistance to Inhibition of Drug Resistance

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Part of the Soft and Biological Matter book series (SOBIMA)

Abstract

This chapter exploits systems biology annotation and combines it with the wrapping technology. The chapter focuses on combination drug treatments developed based on epistructural design to enhance therapeutic power and safety beyond the levels achievable through drug monotherapy. The drugs in the combination treatments exert a therapeutic effect and also counteract/antagonize each other in contexts where one of them elicits undesirable side effects or resistance to inhibition of drug resistance.

Keywords

Chronic Myeloid Leukemia Focal Adhesion Kinase Selectivity Filter Primary Drug Inhibitory Impact 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Widakowich C, de Castro G, de Azambuja E, Dinh P, Awada A. Review: side effects of approved molecular targeted therapies in solid cancers. Oncologist. 2007;12:1443–55.CrossRefGoogle Scholar
  2. 2.
    Schmidinger M, Zielinski CC, Vogl UM, et al. Cardiac toxicity of sunitinib and sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2008;26:5204–12.CrossRefGoogle Scholar
  3. 3.
    Lacouture ME. Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer. 2006;6:803–12.CrossRefGoogle Scholar
  4. 4.
    Verheul HM, Pinedo HM. Possible molecular mechanisms involved in the toxicity of angiogenesis inhibition. Nat Rev Cancer. 2007;7:475–85.CrossRefGoogle Scholar
  5. 5.
    Force T, Krause D, van Etten RA. Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition. Nat Rev Cancer. 2007;7:332–44.CrossRefGoogle Scholar
  6. 6.
    Force T, Kerkela R. Cardiotoxicity of the new cancer therapeutics—mechanisms of, and approaches to, the problem. Drug Discov Today. 2008;13:778–84.CrossRefGoogle Scholar
  7. 7.
    Kerkela R, Grazette L, Yacobi R, et al. Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat Med. 2006;12:908–16.CrossRefGoogle Scholar
  8. 8.
    Chu TF, Rupnick MA, Kerkela R, et al. Cardiotoxicity associated with tyrosine kinase inhibitor sunitnib. Lancet. 2007;370:2011–9.CrossRefGoogle Scholar
  9. 9.
    Fernández A, Crespo A, Tiwari A. Is there a case for selectively promiscuous anticancer drugs? Drug Discov Today. 2009;14:1–5.CrossRefGoogle Scholar
  10. 10.
    Zhang X, Crespo A, Fernández A. Turning promiscuous kinase inhibitors into safer drugs. Trends Biotechnol. 2008;26:295–301.CrossRefGoogle Scholar
  11. 11.
    Dancey J, Sausville EA. Issues and progress with protein kinase inhibitors for cancer treatment. Nat Rev Drug Discov. 2003;2:296–313.CrossRefGoogle Scholar
  12. 12.
    Levitzki A, Gazit A. Tyrosine kinase inhibition: an approach to drug development. Science. 1995;267:1782–8.ADSCrossRefGoogle Scholar
  13. 13.
    Fernández A, Sanguino A, Peng Z, Ozturk E, Chen J, Crespo A, Wulf S, Shavrin A, Qin C, Ma J, Trent J, Lin Y, Han HD, Mangala LS, Bankson JA, Gelovani J, Samarel A, Bornmann W, Sood AK, Lopez-Berestein G. An anticancer c-kit kinase inhibitor is reengineered to make it more active and less cardiotoxic. J Clin Invest. 2007;117:4044–54.CrossRefGoogle Scholar
  14. 14.
    Kitano H. A robustness-based approach to systems-oriented drug design. Nat Rev Drug Discov. 2007;6:202–9.CrossRefGoogle Scholar
  15. 15.
    Torchilin VP. Multifunctional nanocarriers. Adv Drug Deliv Rev. 2006;58:1532–55.CrossRefGoogle Scholar
  16. 16.
    Langer R. Drug delivery: drugs on target. Science. 2001;293:58–9.CrossRefGoogle Scholar
  17. 17.
    Allen TM, Cullis PR. Drug delivery systems: entering the mainstream. Science. 2004;303:1818–22.ADSCrossRefGoogle Scholar
  18. 18.
    Deninger M, Buchdunger E, Druker BJ. The development of imatinib as a therapeutic agent for chronic myeloid leukemia. Blood. 2005;105:2640–53.CrossRefGoogle Scholar
  19. 19.
    Dancey JE, Chen HX. Strategies for optimizing combinations of molecularly targeted anticancer drugs. Nat Rev Drug Discov. 2006;5:649–59.CrossRefGoogle Scholar
  20. 20.
    Keith CT, Borisky AA, Stockwell BR. Multicomponent therapeutics for networked systems. Nat Rev Drug Discov. 2005;4:71–8.CrossRefGoogle Scholar
  21. 21.
    Zimmermann GR, Lehar J, Keith CT. Multi-target therapeutics: when the whole is greater than the sum of the parts. Drug Discov Today. 2007;12:34–42.CrossRefGoogle Scholar
  22. 22.
    Verweij J, Casali P, Kotasek D, et al. Imatinib does not induce cardiac left ventricular failure in gastrointestinal stromal tumours patients: analysis of EORTC-ISG-AGITG study 62005. Eur J Cancer. 2007;43:974–8.CrossRefGoogle Scholar
  23. 23.
    Atallah E, Durand JB, Kantarjian H, Cortes J. Congestive heart failure is a rare event in patients receiving imatinib. Blood. 2007;110:1233–7.CrossRefGoogle Scholar
  24. 24.
    Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007;356:125–34.CrossRefGoogle Scholar
  25. 25.
    O’Neill E, Rushworth L, Baccarini M, Kolch W. Role of the kinase MST2 in suppression of apoptosis by the proto-oncogene product Raf-1. Science. 2004;306:2267–70.ADSCrossRefGoogle Scholar
  26. 26.
    Dhillon AS, Hagan S, Rath O, Kolch W. MAP kinase signalling pathways in cancer. Oncogene. 2007;26:3279–90.CrossRefGoogle Scholar
  27. 27.
    Chen J, Zhang X, Fernández A. Molecular basis for specificity in the druggable kinome: sequence-based analysis. Bioinformatics. 2007;23:563–72.CrossRefGoogle Scholar
  28. 28.
    Faivre S, Demetri G, Sargent W, Raymond E. Molecular basis for sunitinib efficacy and future clinical development. Nat Rev Drug Discov. 2007;6:734–45.CrossRefGoogle Scholar
  29. 29.
    O’Neill EE, Matallanas D, Kolch W. Mammalian sterile 20-like kinases in tumor suppression: an emerging pathway. Cancer Res. 2005;65:5485–7.CrossRefGoogle Scholar
  30. 30.
    Karaman MW, Herrgard S, Treiber DK, et al. A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol. 2008;26:127–32.CrossRefGoogle Scholar
  31. 31.
    Kantarjian H, Jabbour E, Grimley J, Kirkpatrick P. Dasatinib. Nat Rev Drug Discov. 2006;5:717–8.CrossRefGoogle Scholar
  32. 32.
    Fernández A, Sessel S. Selective antagonism of anticancer drugs for side effect removal. Trends Pharmacol Sci. 2009;30:403–10.CrossRefGoogle Scholar
  33. 33.
    Halder J, Lin YG, Merritt WM, Spannuth WA, Nick AM, Honda T, Kamat AA, Han LY, Kim TJ, Lu C, Tari AM, Bornmann W, Fernandez A, Lopez-Berestein G, Sood AK. Therapeutic efficacy of a novel focal adhesion kinase inhibitor TAE226 in ovarian carcinoma. Cancer Res. 2007;67:10976–83.CrossRefGoogle Scholar
  34. 34.
    Vivas-Mejia P, Benito JM, Fernández A, Han HD, Mangala L, Rodriguez-Aguayo C, Chavez-Reyes A, Lin YG, Carey MS, Nick AM, Stone RL, Kim HS, Claret FX, Bornmann W, Hennessy BT, Sanguino A, Peng Z, Sood AK, Lopez-Berestein G. c-Jun-NH2-kinase-1 inhibition leads to antitumor activity in ovarian cancer. Clin Cancer Res. 2010;16:184–94.CrossRefGoogle Scholar
  35. 35.
    Martz CA, Ottina KA, Singleton KR, Jasper JS, Wardell SE, Peraza-Penton A, Anderson GR, Winter PS, Wang T, Alley HM, Kwong LN, Cooper ZA, Tetzlaff M, Chen PL, Rathmell JC, Flaherty KT, Wargo JA, McDonnell DP, Sabatini DM, Wood KC. Systematic identification of signaling pathways with potential to confer anticancer drug resistance. Sci Signal. 2014;7:ra121.CrossRefGoogle Scholar
  36. 36.
    Muranen T, Selfors LM, Worster DT, Iwanicki MP, Song L, Morales FC, Gao S, Mills GB, Brugge JS. Inhibition of PI3K/mTOR leads to adaptive resistance in matrix-attached cancer cells. Cancer Cell. 2012;21:227–39.CrossRefGoogle Scholar
  37. 37.
    Liang J, Mills GB. AMPK: a contextual oncogene or tumor suppressor? Cancer Res. 2013;73:2929–35.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.National Research Council (CONICET)Buenos AiresArgentina
  2. 2.Rice UniversityHoustonUSA

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