Arzneimittelforschung 2008; 58(6): 261-264
DOI: 10.1055/s-0031-1296504
Review
Editio Cantor Verlag Aulendorf (Germany)

Intrinsic and Acquired Drug Resistance in Malignant Tumors

The main reason for therapeutic failure
Theodor H Lippert
1   Medical Faculty, University of Tuebingen, Germany
,
Hans-Jörg Ruoff
1   Medical Faculty, University of Tuebingen, Germany
,
Manfred Volm
2   German Cancer Research Center, Heidelberg, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
15 December 2011 (online)

Abstract

Drug resistance is the major reason for failure in cancer chemotherapy. Resistance may be either pre-existent (intrinsic resistance), or induced by drugs (acquired resistance).

So far, no strategy has been found to overcome resistance, which is based on highly complex and individually variable biological mechanisms. In present clinical practice, drug resistance can only be recognized during treatment, after long lag times. Thus diagnostic tests are required, indicating resistance at an earlier stage, in order to avoid unnecessary medication, frequently associated with toxic side-effects.

A number of new anti-cancer drugs are now available. In contrast to the unspecifically acting cytostatic chemotherapy, these compounds have targeted actions. However, as recent studies have shown, resistances and severe side-effects can also be found with targeted drugs.

With the increasing number of new treatment regimens, the early diagnosis of resistance will optimize therapy, and indeed will be indispensable for individual cancer therapy.

The resistance assays available for use in clinical practice should be integrated into cancer therapy. Research into this neglected area needs to be intensified.

 
  • References

  • 1 Sikora K. Paying for cancer care – a new dilemma. J Roy Soc Med. 2007; 100: 166-169
  • 2 Bosanquet N, Sikora K. The Economics of Cancer Care. Cambridge: Cambridge University Press; 2006
  • 3 Volm M, Koomagi R, Efferth T. Prediction of drug sensitivity and resistance of cancer by protein expression profiling. Cancer Genom Proteom. 2004; 1: 157-166
  • 4 Volm M. Multidrug resistance and its reversal. Anticancer Res. 1998; 18: 2905-2918
  • 5 Efferth T, Volm M. Pharmacogenetics for individual cancer chemotherapy. Pharmacol Ther. 2005; 107: 155-176
  • 6 Verheul HMW, Pinedo HM. Clinical implications of drug resistance. In Pinedo HM, Giaccone G. editors Drug Resistance in the Treatment of Cancer. Cambridge: Cambridge University Press; 2006. p 199-231
  • 7 Dawson M, Dryden WF. Tissue culture in the study of the effects of drugs. J Pharm Sci. 1967; 56: 545-561
  • 8 Tanneberger S. Gewebekultur und Krebschemotherapie. Arch Geschwulstforsch. 1968; 31: 387-400
  • 9 Dendy PP, Hill BT. Human Tumour Drug Sensitivity Testing In Vitro. London: Academic Press; 1983
  • 10 Weisenthal LM. Predictive assays for drug und radiation resistance. In Masters JRW. editor Human Cancer in Primary Culture. Dordrecht: Kluwer Academic Publishers; 1991. p 103-147
  • 11 Dickson RB, Lippman ME. Drug and Hormonal Resistance in Breast Cancer. New York: Ellis Horwood; 1995
  • 12 Reinhold U, Tilgen W. Chemosensitivity Testing in Oncology. Berlin: Springer; 2003
  • 13 Blumenthal RD. Chemosensitivity. Volume I, In Vitro Assays and Volume 2, In Vivo Models, Imaging and Molecular Regulators. Totowa, New Jersey: Humana Press; 2005
  • 14 Diamandis EP, Fritsche HA, Lilja H, Chan DW, Schwartz MK. Tumor Markers. Physiology, Pathobiology, Technology, and Clinical Applications. Washington DC: AACC Press; 2002
  • 15 Endo K, Oriuchi N, Higuchi T, Jida Y, Hanaoka H, Miyakubo M et al. PET and PET/CT using 18F-FDG in the diagnosis and management of cancer patients. Int J Clin Oncol. 2006; 11: 286-296
  • 16 Weber WA, Figlin R. Monitoring cancer treatment with PET/CT: does it make a difference?. J Nucl Med. 2007; 48 (Suppl 1) 365-445
  • 17 Jerusalem G, Belhocine TC. Metabolic monitoring of chemosensitivity with 18 FDG PET. In Blumenthal RE. editor Chemosensitivity Volume 2, In Vivo Models, Imaging and Molecular Regulators. Totowa, New Jersey: Humana Press; 2005. p 417-440
  • 18 Osipo C, O’Regan RM. Resistance to antiestrogens. In Teicher BA. editor Cancer Drug Resistance. Totowa, New Jersey: Humana Press; 2006. p 413-433
  • 19 Michalides R, Griekspoor A, Balkenende A, Verwoerd D, Janssen L, Jalink K. Tamoxifen resistance by a conformational arrest of the estrogen receptor alpha after PKA activation in breast cancer. Cancer Cell. 2004; 5: 597-605
  • 20 Nathan DG. The Cancer Treatment Revolution: How Smart Drugs and Other New Therapies Are Renewing Our Hope and Changing the Face of Medicine. Hoboken, New Jersey: John Wiley & Sons; 2007
  • 21 Lan K-H, Lu C-H, Yu D. Mechanisms of trastuzumab resistance and their clinical implications. Ann NY Acad Sci. 2005; 1059: 70-75
  • 22 Sweetman SC. Martindale. The Complete Drug Reference. London: Pharmaceutical Press; 2007
  • 23 Bast RC, Zalutsky MR, Kreitman RJ, Frankel AE. Monoclonal serotherapy. In Kufe DM, Bast RC, Hait WN. et al, eds Cancer Medicine. London: BC Decker Inc; 2006. p 770-785
  • 24 Widakowich C, de Castro G, de Azambuja E, Dink P, Awoda A. Review: side-effects of approved molecular targeted therapies in solid cancers. Oncologist. 2007; 12: 1443-1455
  • 25 Sartore-Bianchi A, Ricotta R, Cerea G, Maugeri MR, Siena S. Rationale and clinical results of multi-targeted treatments in oncology. Int J Biol Markers. 2007; 22 (I Suppl 4) S77-S87
  • 26 Schrag D, Garewal HS, Burstein HJ, Samson DJ, Von Hoff DD, Somerfield MR. American Society of Clinical Oncology Technology Assessment: Chemotherapy Sensitivity and Resistance Assays. J Clin Oncol. 2004; 22: 3631-3638