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Uterine Cancer: The Influence of Genetics and Environment on Cell Cycling Pathways in Cancer

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Book cover Biotargets of Cancer in Current Clinical Practice

Part of the book series: Current Clinical Pathology ((CCPATH))

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Abstract

Endometrial cancer is the most common gynecologic malignancy in the USA and is becoming increasingly more prevalent in industrialized countries. Endometrial cancer accounts for over 43,000 new cases (6% of all cancer cases) and almost 8,000 deaths annually (3% of cancer deaths). This chapter reviews current knowledge about endometrial cancer and its implication for strategies at prevention and treatment, with a particular focus on molecular mechanisms of pathogenesis and targeted therapies.

Endometrial cancer presents as abnormal uterine bleeding, with 80% of cases occurring in postmenopausal patients. The disease is further subcategorized as type I or II. Type I is associated with unopposed estrogen and an endometrioid histology, whereas type II is a more aggressive subtype that presents at a later stage, generally demonstrates a serous histology, and is more likely to recur.

Genetic mutations play a key role in the development of endometrial cancer. Hereditary syndromes such as HNPCC and Lynch syndrome and their germ line mutations have been well described. Various somatic mutations play an important role on tumorigenesis and poor clinical outcomes, such as loss of function of tumor suppressor genes. Further investigation of cell signaling pathways provides novel insights into mechanisms of disease as well as providing therapeutic targets. Current knowledge about the role of tumor suppressor genes, TP53 and PTEN, and mutations in key cell signaling pathways, such as the PI3K-Akt-mTOR pathway, is discussed.

Translational implications for endometrial cancer therapy, traditional chemotherapies, and potential advantages of novel, targeted agents such as mTOR, VEGF, and PI3K inhibitors are reviewed. To date, none of these targeted therapies have demonstrated response rates approaching those of conventional therapies, but they have added greatly to our understanding of endometrial cancer pathogenesis and clinical correlations with disease recurrence and resistance to chemotherapy.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Massachusetts General Hospital, Yawkey 9E Women’s Cancer Center, 55 Fruit Street, Boston, MA, 02114, USA

    Annekathryn Goodman M.D. & Leslie A. Garrett M.D.

  2. Division of Gynecologic Oncology, Massachusetts General Hospital, Boston, MA, USA

    Leslie S. Bradford M.D.

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Correspondence to Annekathryn Goodman M.D. .

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  1. Chair of General Pathology, Department of Experimental Medicine, University of L’Aquila, Via Vetoio, Coppito-2, L'Aquila, 67100, Italy

    Mauro Bologna

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Goodman, A., Bradford, L.S., Garrett, L.A. (2012). Uterine Cancer: The Influence of Genetics and Environment on Cell Cycling Pathways in Cancer. In: Bologna, M. (eds) Biotargets of Cancer in Current Clinical Practice. Current Clinical Pathology. Humana Press. https://doi.org/10.1007/978-1-61779-615-9_15

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  • DOI: https://doi.org/10.1007/978-1-61779-615-9_15

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  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-614-2

  • Online ISBN: 978-1-61779-615-9

  • eBook Packages: MedicineMedicine (R0)

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