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Tumor Suppressor Par-4 pp 41–58Cite as

Par-4 in Chemoresistant Ovarian and Endometrial Cancers

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Abstract

Ovarian cancer is the most lethal gynecological cancer; on the other hand, endometrial cancer is the most prevalent, with exceedingly poor prognostic when found to be recurring. In both cases, robust resistance to chemotherapeutic compounds, may they be genotoxic in nature or specifically targeting dysregulated pathways, drastically reduce our ability to treat these diseases. In order to overcome the chemoresistant nature of these neoplastic entities, novel therapeutic avenues must be explored. In that context, Par-4, a pro-apoptotic protein that has been reported to selectively induce cell suicide in cancer cells, appears to be of particular interest. This review aims to objectively assemble the available evidence, which predominantly emanates from non-gynecological tissues, and underline the convergent findings of past investigations, highlight divergences, and help direct future research endeavors. Considering that both of these tumors are characterized by prevalent mutations in the PI3K/Akt/PTEN axis as well as alterations in p53, our work provides a sharp focus on the regulatory role of these molecular pathways on Par-4 function. We hope this chapter will allow the potent abilities of Par-4 to be fully leveraged in these tissular contexts and augment the available armamentarium, so that we may eventually improve the prognostic of women afflicted with these diseases.

Keywords

  • Par-4
  • Chemoresistant tumors
  • Ovarian cancer
  • Endometrial cancer
  • Pathogenesis
  • Molecular mechanisms
  • Gynecological tissues
  • PI3K/Akt/mTOR axis
  • NF-kappaB
  • p53
  • Autophagy

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  1. Department of Medical Biology, Université du Québec à Trois-Rivières, Trois-Rivières, QC, Canada

    François Fabi, Pascal Adam & Eric Asselin

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  1. François Fabi
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  2. Pascal Adam
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    Ph.D. Vivek M. Rangnekar

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Fabi, F., Adam, P., Asselin, E. (2021). Par-4 in Chemoresistant Ovarian and Endometrial Cancers. In: Rangnekar, V.M. (eds) Tumor Suppressor Par-4. Springer, Cham. https://doi.org/10.1007/978-3-030-80558-6_3

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