Clinical & Experimental Metastasis

, Volume 35, Issue 4, pp 309–318 | Cite as

The challenge of drug resistance in cancer treatment: a current overview

  • Michail Nikolaou
  • Athanasia Pavlopoulou
  • Alexandros G. Georgakilas
  • Efthymios KyrodimosEmail author
Research Paper


It is generally accepted that recent advances in anticancer agents have contributed significantly to the improvement of both the disease-free survival and quality of life in cancer patients. However, in many instances, a favorable initial response to treatment changes afterwards, thereby leading to cancer relapse and recurrence. This phenomenon of acquired resistance to therapy, it is a major problem for totally efficient anticancer therapy. The failure to obtain an initial response reflects a form of intrinsic resistance. Specific cell membrane transporter proteins are implicated in intrinsic drug resistance by altering drug transport and pumping drugs out of the tumor cells. Moreover, the gradual acquisition of specific genetic and epigenetic abnormalities in cancer cells could contribute greatly to acquired drug resistance. A critical issue in the clinical setting, is that the problem of drug resistance appears to have a negative effect on also the new molecularly-targeted anticancer drugs. Several ongoing efforts are being made by the medical community aimed to the identification of such resistance mechanisms and the development of novel drugs that could overcome them. In this review, the major drug resistance mechanisms and strategies to overcome them are critically discussed, and also possible future directions are suggested.


Drug resistance Acquired resistance Chemotherapy resistance Multidrug resistance Tumor microenvironment Cancer 



Multidrug resistance


Adenosine triphosphate-binding cassette


Dihydrofolate reductase


Nucleotide excision repair


Maximum tolerated dose



Dr. A.G. Georgakilas acknowledges funding from DAAD Grant “DNA Damage and Repair and Their Relevance to Carcinogenesis” (No. 57339330).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Internal Medicine, Oncology Unit, Hippokrateio HospitalUniversity of AthensAthensGreece
  2. 2.Izmir International Biomedicine and Genome InstituteDokuz Eylül UniversityIzmirTurkey
  3. 3.DNA Damage Laboratory, Department of Physics, School of Applied Mathematical and Physical SciencesNational Technical University of Athens (NTUA)AthensGreece
  4. 4.1st Department of Otolaryngology Head and Neck Surgery, Hippokrateio HospitalNational and Kapodistrian University of Athens11527 AthensGreece

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