Current Status of Methods to Assess Cancer Drug Resistance

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.

Mesenchymal stem cell-mediated cancer therapy: A dual-targeted strategy of personalized medicine

“…Since the beginning of cancer chemotherapy the frequent lack of drug response in solid tumors has been a major problem. In nearly 50% of all cancer cases, resistance to chemotherapy already exists before drug treatment starts (intrinsic resistance), and in a large proportion of remaining cases drug resistance develops during the treatment (acquired resistance) [73] . The mechanisms contributing to multidrug resistance phenotype and the challenges facing molecular targeted therapy were discussed in a recent review [74] .…”

EGFR inhibition evokes innate drug resistance in lung cancer cells by preventing Akt activity and thus inactivating Ets-1 function

“…The remaining patients respond, but only partially, even though they too have EGFR mutations. We speculate that this limited primary response may be attributable to resistance inherent in the tumor cells even before treatment begins and not to resistance acquired over its course (4).…”

Influence of resistance to 5-fluorouracil and tomudex on [18F]‑FDG incorporation, glucose transport and hexokinase activity

“…A rapid means of determining drug response status of tumours to chemotherapy agents has been recognised as an essential clinical tool for decades (12). Methods with the potential of determining potential responders include fresh tumour cell culture, predictive molecular biomarkers in biofluids prior to or at early treatment time-points and imaging biomarkers, such as those obtained with functional imaging modalities, for example PET.…”