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Rational Design of DNA Anticancer Agent That Targets Signal Transducer and Activator of Transcription 3 (Stat3) for Cancer Therapy

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Cell Signaling & Molecular Targets in Cancer

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Abstract

Signal transducer and activator of transcription 3 (Stat3) has been identified as an important target for cancer therapy, since it participates in oncogenesis through the upregulation of genes encoding apoptosis inhibitors (Bcl-xL, Bcl-2, Mcl-1, and survivin), cell-cycle regulators (cyclin D1 and c-myc), and inducers of angiogenesis (VEGF). Also, Stat3 is constitutively activated in many human cancers. Moreover, recent studies have demonstrated that Stat3 is constitutively activated both in tumor cells and in immune cells in the tumor microenvironment. Targeting Stat3 is expected to decrease the survival and angiogenic potential not only in tumor cells but also in immune cells in the tumor stroma. We have laid the groundwork for the development of the G-rich oligodeoxynucleotide (GQ-ODN) T40214 as a potent inhibitor of Stat3 activity. Our studies demonstrated that T40214 represents a novel anti-cancer agent based on: (a) selective inhibition of Stat3 activity in vitro and in vivo, (b) significant suppression of tumor growth and increased survival time in a nude mouse xenograft model of prostate cancer, (c) T40214 transport using a novel and effective intracellular delivery system, and (d) low toxicity of T40214. Here we introduce the developed Stat3 inhibitors and review the rational development of T40214 as a novel Stat3 inhibitor by providing previous experimental results.

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Acknowledgments

Author greatly appreciates all the post doctors, staffs, and collaborators who made contributions to develop GQ-ODN T40214 as an anticancer agent. This project was mainly supported by grants DOD PC020407 and R01 CA104035.

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  1. Department of Medicine, Baylor College of Medicine, Houston, TX, 77030, USA

    Naijie Jing Ph.D

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Correspondence to Naijie Jing Ph.D .

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  1. , Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India

    Malay Chatterjee

  2. , Division of Biochemistry & Chemistry, City University of New York Medical Scho, New York, 10031, New York, USA

    Khosrow Kashfi

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Jing, N. (2012). Rational Design of DNA Anticancer Agent That Targets Signal Transducer and Activator of Transcription 3 (Stat3) for Cancer Therapy. In: Chatterjee, M., Kashfi, K. (eds) Cell Signaling & Molecular Targets in Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0730-0_8

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