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Emerging Therapeutic Targets for Pancreatic Cancer

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Pancreatic Cancer

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Abstract:

Pancreatic cancer remains a leading cause of cancer mortality in the United States, however a number of novel molecular targets have emerged that offer promising new therapeutic options for this deadly disease. For instance, inhibition of various transcription factors has demonstrated therapeutic potential in preclinical studies. The transcription factors discussed include nuclear factor kappa B, transforming growth factor β, specificity protein 1, and Gli1. Another important area of research involves preventing the phenotypic switch known as the epithelial-to-mesenchymal transition (EMT) that affects the invasive potential of cancer cells. Targeting the hepatocyte growth factor and its receptor c-Met may reverse EMT and also results in decreased pancreatic cancer growth and may provide a means to reverse chemoresistance to gemcitabine. Furthermore, the DNA repair pathway involves various genes including BRCA2 that are involved in homologous recombination, and CHEK-1/2, a cell cycle checkpoint kinase, both of which provide opportunities for individualizing pancreatic cancer treatment in patients with alterations in these pathways. Preclinical data have shown that BRCA2 mutants are more sensitive to traditional cytotoxic agents, including cisplatin, while specific polymorphisms in CHEK-1, as an example, strengthen gemcitabine’s utility as a radiosensitizer in patients with locally-advanced pancreatic cancer. Also of interest, the proteasome inhibitor bortezomib causes endoplasmic reticulum stress in vitro and in vivo, thereby activating apoptosis in pancreatic cancer cells. Finally, advances in gene therapy will be discussed as this provides a mechanism for targeting pancreatic cancer cells with potentially few side effects.

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  1. Department of Gastrointestinal Medical Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX, USA

    Rachna T. Shroff & James L. Abbruzzese

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  1. Rachna T. Shroff
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  2. James L. Abbruzzese
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Shroff, R.T., Abbruzzese, J.L. (2010). Emerging Therapeutic Targets for Pancreatic Cancer. In: Pancreatic Cancer. Springer, New York, NY. https://doi.org/10.1007/978-0-387-77498-5_54

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