Diagnosis of cancer multidrug resistance by bacterium-mediated imaging Omar Anwar Elkadi a,b,⇑ , Muhammad Abdelbasset a a Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt b Department of Oncology, Dar Elsalam Hospital, Cairo, Egypt article info Article history: Received 8 April 2015 Accepted 26 January 2016 abstract Multidrug resistance (MDR) is a phenomenon expressed by many tumors affecting the chemotherapy efficacy, treatment decision, and the disease prognosis. Considering its great implication, non-invasive approaches are needed to identify this phenomenon in early stages of the disease. This article discusses the potential of the emerging non-invasive bacterium-mediated imaging of cancer in diagnosis of MDR. This potential is derived from the effect of cancer MDR on the pharmacokinetics of certain antibiotics, which are substrates of the MDR proteins. Since MDR proteins actively pump their substrates outside the resistant cancer cells, the elimination of the employed reporter bacteria, proliferating within MDR cancer cells, would require a larger dose of these antibiotics compared to those inside non-MDR cancer cells. These bacteria bear reporter genes that produce specific signals such as bioluminescent, fluorescent, magnetic, or radioactive signals that can be detected by non-invasive imaging modalities. Therefore, the presence, degree, and mechanism of MDR can be estimated by comparing the concentration of the employed antibiotic, required to cease these signals (reflecting the elimination of the bacteria), to a pre-determined reference. The real time imaging of MDR cancer and the early diagnosis of MDR, offered by this approach, would provide a better tool for preclinical studies of MDR, and allow a prompt choice of the most appropriate therapy. Ó 2016 Elsevier Ltd. All rights reserved. Introduction Multidrug resistance Multidrug resistance (MDR) is a phenomenon expressed by many tumors, representing the main cause of chemotherapy fail- ure. MDR is defined as the intrinsic or acquired resistance of cancer cells to structurally and functionally unrelated drugs [1]. Many mechanisms are involved in MDR including Adenosine triphos- phate Binding Cassette (ABC) transporters up-regulation [2–4] and limited drug penetration in solid tumors [5]. ABC transporters up-regulation and the significance of multidrug resistance ABC transporters, especially P-glycoprotein (Pgp) and Multi Drug Resistance associated protein (MRP), are major contributors to MDR. They work by an efflux mechanism maintaining a very low concentration of their substrates (such as chemotherapeutic agents), insufficient to carry out their effect [3,6]. These proteins are usually over-expressed in patients refractory to chemotherapy; this overexpression is generally associated with poor prognosis [2,4,7]. Thus, MDR phenotype can affect the treatment decision of cancer. For instance, if the tumor is MDR, then one of three strategies should be considered during therapy: avoiding the MDR pumps, using drugs that are not substrate of the pumps; reversing the resistance, using MDR pump inhibitors [4,8]; or even exploiting it, using protector drugs substrate to the MDR pumps [6,8]. Cancer multidrug resistance and antibacterial chemotherapy Cancer MDR implication goes beyond cancer to affect antibacterial chemotherapy. Since MDR reduces the intracellular accumulation of some antibiotics (substrate of the MDR pumps), it reduces their activity against intracellular bacteria: increasing their minimum inhibitory concentration (MIC) [6,9]. These antibiotics are diverse including and belong to various classes: macrolides, azalides, ciprofloxacin, ofloxacin, clindamycin, rifampicin, chloramphenicol, doxycycline, and trimethoprim [9,10]. Again, MRP and Pgp play an important role in this reduced http://dx.doi.org/10.1016/j.mehy.2016.01.016 0306-9877/Ó 2016 Elsevier Ltd. All rights reserved. Abbreviations: MDR, multidrug resistance; ABC, Adenosine triphosphate Binding Cassette; Pgp, P-glycoprotein; MRP, multidrug resistance associated protein; MIC, minimum inhibitory concentration; [ 99m Tc] MIBI, technetium labeled sestamibi; MRI, magnetic resonance imaging; PET, positron emission tomography; BLI, bioluminescent imaging; FLI, fluorescent imaging. ⇑ Corresponding author. Tel.: +20 102666595. E-mail address: Omar.elkadi@live.com (O.A. Elkadi). Medical Hypotheses 89 (2016) 11–15 Contents lists available at ScienceDirect Medical Hypotheses journal homepage: www.elsevier.com/locate/mehy