Mini Review
Volume 8 Issue 2 - 2020
Co-expression of MRP1 and STAT3 in Various Type of Cancers May Indicate Constitutive Resistance to Cancer Chemotherapy
Paiboon Jungsuwadee*
Department of Pharmaceutical Sciences, Fairleigh Dickinson University, School of Pharmacy and Health Sciences, Florham Park, NJ, USA
*Corresponding Author: Paiboon Jungsuwadee, Department of Pharmaceutical Sciences, Fairleigh Dickinson University, School of Pharmacy and Health Sciences, Florham Park, NJ, USA.
Received: October 10, 2019; Published: January 10, 2020




Abstract

Cancer resistance is a major hurdle for cancer treatment. Understanding how cancers become resistant to chemotherapeutic agents i.e. mechanisms underlying the resistance is pivotal to a success of cancer chemotherapy. Multidrug-resistant associated protein 1 (MRP1) and signal transducer and transcription activator 3 (STAT3) are two factors, in addition to other factors, that play significant roles in cancer biology and cancer resistance. Both MRP1 and STAT3 proteins are ubiquitously expressed in various types of tissue. MRP1 is an efflux transporter. Overexpression of MPR1 has been associated with treatment failure in many malignant neoplasia due to a decreased intracellular accumulation of chemotherapeutic agents. STAT3 is a pleiotropic transcription factor, which can be activated through several factors such as growth factors and cytokines via Janus kinase (JAK)-STAT signaling pathways. STAT3 target genes include cyclin D1, Bcl-xL, c-myc, Mcl1, VEGF, reflecting STAT3’s involvement in diverse cellular processes. Additionally, STAT3 can upregulate MRP1 therefore co-expression of MRP1 and STAT3 are often observed in various types of cancers. Hence, the co-expression of MRP1 and STAT3 may suggest a cancer resistant phenotype. Inhibition of STAT3 activation could reverse the resistant phenotype of cancer by obliterating the expression of MRP1. Currently, there is no direct STAT3 inhibitor approved by the US Food and Drug Administration. However, suppressing MRP1 expression can be achieved by blocking IL-6 signaling pathway e.g. by anti-IL-6 monoclonal antibody, tocilizumab. Because IL-6R signaling causes an activation of STAT3, which has been associated with IL-6 induces drug resistance, incorporation of anti-IL-6 into pharmacotherapy regimens may be beneficial to cancer patients. Thus, comprehensive clinical trials, pharmacological and toxicological studies as well as translational researches with regards to cancer resistance and MRP1 and STAT3 expression status are warranted..

Keywords: Multidrug-Resistant Associated Protein 1 (MRP1); Signal Transducer and Transcription Activator 3 (STAT3)

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Citation: Paiboon Jungsuwadee. “Co-expression of MRP1 and STAT3 in Various Type of Cancers May Indicate Constitutive Resistance to Cancer Chemotherapy”. EC Pharmacology and Toxicology 8.2 (2020): 01-04.

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